Monoclonal IgD Research Articles

Case Report: A case of IgD lambda/lambda Multiple Myeloma in patient with acute renal failure and without monoclonal spike in serum electrophoresis

BackgroundIgD Multiple Myeloma is a rare form of plasma cell dyscrasia and accounts for approximately 1-2% of all cases of Multiple Myeloma. It mainly affects young, male subjects; it is characterized by an aggressive course, a high production of Bence Jones protein, acute renal failure and an often unfortunate outcome compared to the other isotypes of MM. A distinctive feature is the lack of a monoclonal peak on serum protein electrophoresis (SPE).Case reporta 57-year-old man with pain in his left lower limb and weight loss goes to the Emergency Department (Emergency Department). Laboratory tests performed showed normocytic normochromic anemia (Hemoglobin 9.4 g/dL), acute renal failure (s-creatinine 2.85 mg/dL, e-GFR 23 mL/min/1.73 m². serum protein electrophoresis (SPE) detected only mild polyclonal in the gamma zone with no evidence of any monoclonal peak.Resultsserum immunofixation (s-IFE) showed a monoclonal IgD λ band and a monoclonal λ band. The Free Light Chains (s-FLC) measurement showed a ratio of 0.04. The bone marrow biopsy confirmed an infiltration of> 20% of clonal plasma cells; renal biopsy diagnosed “cast nephropathy”.ConclusionIgD λ/λ Multiple Myeloma is a rare form of this disease with a poor prognosis; an early and correct laboratory diagnosis is crucial for appropriate treatment and effective monitoring in order to improve patient outcome.

P317 FATAL EVOLUTION IN A YOUNG WOMAN DUE TO AMYLOIDOSIS HEART FAILURE IN A RARE MULTIPLE MYELOMA DISEASE

Abstract Introduction Immunoglobulin (Ig) D (IgD) monoclonal gammopathy is a rare subtype of multiple myeloma (MM) associated with a worse prognosis. Ig light chains amyloidosis is a disorder characterized by extracellular deposition of Ig light chains in various tissues, leading to organ dysfunction. Case A 29–year–old woman was admitted for dyspnea and tachycardia for moderate efforts. Lab revealed hypogammaglobulinemia with a monoclonal IgD K paraprotein. There was an increase in K free chains, with a dramatic increase in K/λ free chains Ratio. Proteinuria was 1360 mg/24h with a free K chains Bence Jones Protein. An increase in values of Troponin–I (137,5 pg/mL) and NT–proBNP (12527 pg/mL) pointed towards heart involvement. Furthermore, the ECG showed low voltages in the peripheral leads. Echocardiogram showed a moderate concentric left ventricular hypertrophy with diffused myocardial speckled pattern, an ejection fraction (EF) of 53% and PAPs of 71 mmHg and pericardial effusion. Chest CT scan showed bilateral pleural effusion. Spine MRI and whole body PET/CT indicated areas of osteolytic lesions. Plasma cells infiltration (85% CD138, MUM1 and K chains positivity) was present at bone marrow biopsy. Amyloid deposition was detected in abdominal fat tissue sample. Total bone scintigraphy excluded a transthyretin heart deposition. Thus, amyloidosis associate to IgD MM was diagnosed. In few days heart failure worsened (hs–cTnI 156,6 pg/mL; NT–proBNP 26583 pg/mL, EF 48%,) and the patient began complaining non–productive cough, dyspnea, and columnar edema of the lower limbs. She was not eligible for bone marrow transplantation, so daratumumab, bortezomib, melphalan and prednisone were administered. Despite serological improvement after a short five days course of therapy, she worsened with a further reduction of EF (35%). Blood gas analysis showed hypoxemia and lactate increase quickly turned into a cardiogenic shock. She died by cardiac arrest, just three weeks after admission. Discussion The present case is remarkable for age and gender of the patient as well as the rapid onset and fast worsening of symptoms, which were related to secondary heart amyloid deposition. Symptoms associated to cardiac amyloidosis are expressions of right heart involvement. The early good results of the therapy did not turn the evolution of disease. The fatal and overwhelming progression of the myocardial involvement led to the patient’s death in less than one month.

A rare case of IgE kappa monoclonal gammopathy of undetermined significance identified in a Swedish female

Monoclonal gammopathies involving immunoglobulin E (IgE) is a very rare phenomenon, with less than 70 cases being previously described in the literature. The IgE monoclonal gammopathies include malignant plasma cell disorders such as IgE multiple myeloma (MM), as well as the associated premalignant condition IgE monoclonal gammopathy of undetermined significance (MGUS). We report a case of a 41-year-old woman presenting with an IgE kappa monoclonal protein following routine laboratory testing. Serum protein electrophoresis (SPEP) initially showed a monoclonal protein in the beta-2 fraction, at an estimated concentration of <4 g/L. Subsequent serum immunofixation electrophoresis (SIFE) including antisera to Ig heavy chains delta and epsilon confirmed the presence of an IgE kappa monoclonal protein. Analysis of serum free light chains (FLCs) showed increased levels of kappa FLC, resulting in an abnormally elevated kappa/lambda FLC ratio. No Bence–Jones proteinuria was present. Bone marrow aspiration showed 6% plasma cells, and no sign of myeloma-associated end-organ damage was evident. Consequently, the patient was diagnosed with IgE kappa MGUS. In the present report, the clinical characteristics of the patient are compared to previous descriptions of IgE monoclonal gammopathy. The report further emphasizes the importance of considering the presence of monoclonal IgD or IgE when SIFE shows a clear band positive for a light chain but is negative for Ig heavy chains gamma, alpha and mu.

Myeloma cast nephropathy with diffuse amyloid casts without systemic amyloidosis: two cases report

BackgroundMultiple myeloma (MM) is a plasma-cell derived hematologic malignant disease. The malignant proliferating plasma cells secrete massive monoclonal immunoglobulins which lead to various pathologic types of renal injury. Myeloma cast nephropathy (MCN) is the most common histopathologic lesion with the worst renal prognosis. Rarely, the free light chains in the protein casts can form amyloid fibrils. Here, we reported two rare cases of MCN with diffuse amyloid casts.Case presentationCase 1: A 54-year-old Chinese man presented with a 4-year history of multiple myeloma, proteinuria and hematuria. He had monoclonal IgAλ plus free λ spike in both serum and urine. He had been on chemotherapy for 4 years and maintained normal serum creatinine until 11 months ago. Then, his renal function deteriorated and he went on hemodialysis 4 months before admission. Renal biopsy showed diffuse amyloid casts in the tubular lumens, without any obvious amyloid deposits in other kidney compartments or signs of extra-renal amyloidosis. The amyloid fibrils formed around mononuclear cells which were CD68 negative. According to the morphology and location, these mononuclear cells were considered as tubular epithelial cells. The patient was maintained on chemotherapy and hemodialysis. He died 8 months after renal biopsy.Case 2: A 58-year-old Chinese man presented with a one-and-a-half-year history of proteinuria and slowly rising serum creatinine. He had monoclonal IgDλ spike in both serum and urine. Amyloid casts were observed in the tubular lumens and mononuclear cells could be identified in the center of some casts. There were no amyloid deposits in other kidney compartments and no sign of systemic amyloidosis. The patient also had fine granular deposits along the tubular basement membrane with λ linear staining along tubular basement membrane suggesting light chain deposition disease. He was treated with bortezomib-based chemotherapy followed by lenalidomide-based chemotherapy and achieved very good partial remission (VGPR). After 27 months of follow-up, the patient still showed no signs of systemic amyloidosis.ConclusionsThese 2 cases of MCN with diffuse amyloid casts have different histopathologic characteristics from the usual myeloma casts and tubular epithelial cells might play important roles in the pathogenesis.

Myeloma with biclonal IgG lambda and IgD kappa in serum : a case report

Event Abstract Back to Event Myeloma with biclonal IgG lambda and IgD kappa in serum : a case report Sana Khlif1* 1 Department of Immunology Habib Bourguiba university hospital, Tunisia IgD myeloma is a rare entity (1-3%). Kappa subtype contributes only 10-30% of IgD myelomas and biclonal gammopathies involving IgD are even more rare. In fact, biclonal bands constitute only 3-4% of all myelomas. Case report : We report the case of a 57 years old women, who presented inflammatory low back pain and experienced a severe decline in general health. The symptoms were present 3 months before diagnosis. Laboratory test abnormalities included an elevated erythrocyte sedimentation rate (100mm /h), normochromic normocytic aplastic anemia, hypercalcemia (2,92 mmol/l), hyper-β2-microglobulin (2,87 mg/l). Serum protein electrophoresis showed hypergammaglobulinemia with a monoclonal peak in gamma region. Immunofixation detected an IgD Kappa band and a faint IgG lambda one. Bone marrow aspirated from the sternum was found to contain 30% of malignant plasma cells. Radiograph magnetic resonance imaging (MRI) disclosed myelomateous infiltration of dorsolumber spine and spondylolisthesis, with no evidence of spinal cord compression. IgD myeloma is a particular severe form of myeloma often associated with poor prognosis. The pathogenesis is unclear. This case presents interesting findings regarding prognosis: We discuss, on one side, pronostic significance of biclonal gammopathy with IgD-Κappa comparing to the monoclonal IgD myelomas. On the other side, we analyze particularities of the IgD Kappa compared to the typical IgD lambda. Keywords: biclonal gammapathy, IgD myeloma, kappa subtype, Myeloma Proteins, pronostic Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Khlif S (2013). Myeloma with biclonal IgG lambda and IgD kappa in serum : a case report. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01141 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Aug 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Sana Khlif, Department of Immunology Habib Bourguiba university hospital, sfax, Tunisia, sanakhlif@yahoo.fr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sana Khlif Google Sana Khlif Google Scholar Sana Khlif PubMed Sana Khlif Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The first report of myeloma with IgD κ and free κ in Indonesia

IgD κ myeloma is a rare plasma cell neoplasm case and has never been reported before in Indonesia. In normal condition, IgD level in blood is very low, therefore increase of IgD level in myeloma could be missed by serum protein electrophoresis.A case of a 59 years old female with severe bone pain is reported. In radiology evaluation, there were thoracal compression fracture and thoracal foramen narrowing. For this patient, the myeloma diagnosis was based on WHO criteria, the stage IIIb was based on Durie and Salmon criteria, and bad prognosis with prognostic index stage III diagnosis was based on International Prognostic Index from International Myeloma Working Group, respectively. In serum protein electrophoresis we found a very small monoclonal spike and in immunofi xation there were monoclonal IgD κ and free light chain κ. (Med J Indones 2011; 20:217-21)

Early onset of acute lymphoblastic leukemia with MLL rearrangement after autologous stem cell transplantation for multiple myeloma

Dear Editor, We would like to present our experience with a patient with multiple myeloma (MM) who developed acute lymphoblastic leukemia (ALL) with mixed lineage leukemia gene (MLL) rearrangement only 1 year after administration of alkylating agents. A 61-year-old woman presented with fatigue and was introduced to our hospital in January 2007. Serum immunoelectrophoresis showed increased monoclonal IgD (115.0 mg/dL) and λ light chain, and urine immunoelectrophoresis showed increased monoclonal Bence–Jones protein (4,360 mg/g creatinine). The bone marrow (BM) was infiltrated by malignant plasma cells (50% of nucleated cells) and conventional G-banding cytogenetics revealed normal karyotype (46,XX [20/20]). A diagnosis of MM was made. After four cycles of high-dose dexamethasone, we mobilized and collected her peripheral blood stem cells using cyclophosphamide (4 g/m) and granulocyte-colonystimulating factor in July 2007. She underwent autologous stem cell transplantation (ASCT) in August 2007 with highdose melphalan (200 mg/m) as a conditioning regimen. She made recovery without severe complication. We evaluated the response of treatment as very good partial remission. In July 2008, although she had no symptom, investigation revealed pancytopenia. The BM was heavily infiltrated by blasts (94%) with the immunophenotype as B cell lymphoblasts: CD19+, CD79a+, κ−, l−. G-banding chromosomal cytogenetics revealed chromosomal abnormalities: 46,XX,t(1;11)(p32–34;q23) [4/6]. Fluorescence in situ hybridization (FISH) examination showed split signals of MLL gene. A diagnosis of B-ALL with MLL rearrangement was made. She was commenced on the JALSG 202-O protocol (Clinicaltrials.gov; study ID:NCT00131027) and achieved hematological complete remission. We performed IgH gene rearrangement studies on genomic DNA extracted from the BM aspirates at the time of diagnosis of MM and that of ALL. Southern blotting (SRL inc., Nakagyo-ku, Kyoto, Japan) test showed different monoclonal bands on DNA extracted from both BM aspirates (Fig. 1). From these findings, we concluded that her MM and ALL were derived from different clones. Lau et al. [1] reported a patient with MM that terminated in ALL. Lau indicated that two diseases arose from different clones by IgH gene rearrangement analysis. Cases of secondary ALL supposed to be Topoisomerase II inhibitor-related were previously reported [2], and Lau’s case was administered doxorubicin. Although we did not administer Topoisomerase II inhibitor, we detected chromosomal abnormality of 11q23 that is typically determined from cases of Topoisomerase II inhibitor-related leukemia [2]. To our knowledge, this is the first report describing alkylating-agent-related ALL with MLL rearrangement. Our hypothesis is that her lymphoid progenitor cells had initial instability or a mutation that cannot be detected by conventional G-banding test, and different types of DNA modification separately led to MM and ALL. We suppose modification leading to ALL was MLL rearrangement. This is consistent with the reports that MLL rearrangement is Ann Hematol (2009) 88:813–814 DOI 10.1007/s00277-008-0680-8

Pathologic quiz case: an 81-year-old woman with compression fracture and renal failure. Multiple myeloma with a monoclonal serum IgD lambda immunoglobulin.

Pathologic quiz case: an 81-year-old woman with compression fracture and renal failure. Multiple myeloma with a monoclonal serum IgD lambda immunoglobulin.

Clinico-Pathological Conference

A 53-year-old man was admitted to Keio University Hospital because of serious dyspnea and edema of the lower extremities. Eighteen months previously, the patient had complained of chest discomfort, and was then admitted for the first time to our hospital for evaluation of chest pain. Electrocardiography showed poor R wave progression in leads Vl through V4, and diffuse nonspecific STsegment and T wave abnormalities with low voltage. However, no definitive diagnosis could be made at this initial admission and a calcium-channel blocker was prescribed. Despite this treatment, the patient was readmitted with worsening dyspnea and lower extremity edema. The diagnosis of heart failure and nephritic syndrome was made at the second admission. In addition, immunoelectrophoresis showed a monoclonal IgD (l) M protein and increased plasma cells in the bone marrow, suggesting a diagnosis of multiple myeloma. The patient was thus given dexamethasone (20 mg per day for 4 days) intravenously, but his symptoms did not improve. Two weeks later, the patient deteriorated further with congestive heart failure and renal failure, and subsequently died of cardiac arrest with ventricular fibrillation. On autopsy, IgD (l)-positive plasma cell proliferation was found in the bone marrow, confirming the diagnosis of multiple myeloma. In addition, amyloid deposition was detected in various organs including the heart, kidneys, esophagus, duodenum, ileum, colon, tongue, and lungs. In particular, the weight of the heart was 650 g demonstrating a hypertrophic septum and amyloid deposition in the myocardium and even coronary arteries. In summary, the final diagnosis was IgD (l) multiple myeloma associated with systemic amyloidosis. (Keio J Med 53 (3): 178–191, September 2004)

Enhanced and sustained activation of human B cells by anti-immunoglobulin conjugated to the EBV glycoprotein gp350.

We coupled a monoclonal anti-human IgD to the gp350 gylcoprotein of Epstein-Barr virus, which has been shown to bind to the complement receptor 2 (CR2), and compared its B cell stimulatory ability to that of anti-Ig and to a multivalent anti-Ig-dextran conjugate. The anti-Ig-gp350 conjugate stimulated higher levels of human B cell proliferation in vitro than did anti-Ig or anti-Ig conjugated to control viral protein, comparable to the proliferation stimulated by the multivalent anti-Ig-dextran. This enhanced proliferation was dependent on binding of the conjugate to CR2, inasmuch as an anti-CD2 antibody blocked the enhanced proliferative response. This enhanced proliferative response was associated with prolonged elevations of intracellular ionized calcium, which was comparable to the response stimulated by anti-Ig-dextran. These findings suggest the use of gp350 as a carrier molecule for weakly immunogenic peptides or antigens which, when bound to gp350, would enhance B cell clonal expansion and activation of antigen-specific B cells.

Extramedullary plasmacytoma of the larynx

A case of IgD myeloma in a 54-year-old male with a long-standing history of extramedullary plasmacytoma involving the larynx is reported. The patient was treated with radiation therapy and laryngectomy. Twelve years later, he complained of nasal bleeding. On examination he was found to have large masses in the left nasal cavity and in the left supraclavicular region. Histological examination of both lesions showed plasmacytoma. Serum immunoglobulin studies revealed an IgD monoclonal spike of the lambda type. Bence-Jones protein was present. Using the immunoperoxidase staining technique, cytoplasmic monoclonal IgD was detected.

Differential reactivity of Agaricus bisporus lectin with human IgA subclasses in gel precipitation

The interaction between purified Agaricus bisporus lectin and several human proteins was studied using the Ouchterlony double diffusion and immunoelectrophoresis techniques. Only one precipitation line was observed with normal human serum, normal human colostrum, IgA1 myeloma serum, both serum monoclonal and secretory IgA1 and monoclonal IgD. No reaction was observed with monoclonal and secretory IgA2, IgG, IgM, α 2 macroglobulin or pregnancy-associated α 2 glycoprotein. These results were confirmed by hemagglutination inhibition assays when IgA1, IgA2 and IgD were tested. On the basis of this reactivity, ABL could be a useuseful tool for distinguishing and isolating human IgA subclasses.

Total serum IgD is increased in atopic subjects

We have developed a sandwich-type ELISA system for measuring total IgD levels in the serum of atopics and non-atopic controls. In this ELISA system, affinity purified goat anti-human IgD was used for capture. Results were superior to those obtained with monoclonal anti-human IgD antibody. No cross-reactivity could be demonstrated to IgG, IgM, IgA or IgE. The assay showed minimal non-specific binding even with initial serum dilutions of 1:2. The results obtained were reproducible among replicates (Mean CV +/- SEM = 0.03 +/- 0.002; n = 251), between dilutions (CV = 0.08 +/- 0.006; n = 108), and between assays (CV = 0.05 +/- 0.12; n = 5). We used routine radioimmunoassay for measuring total serum IgE. Using these assays total serum IgD and IgE levels were measured in 75 atopic patients and 33 normal subjects. None of the atopics had recent immunotherapy. As expected, the geometric mean serum IgE in atopics (373 ng/ml) was significantly higher than that in normal subjects (49 ng/ml) (P less than 0.01). However, geometric mean serum IgD was also significantly higher in atopics (20.3 micrograms/ml) than that in normal subjects (8.4 micrograms/ml) (P less than 0.02). In both atopic and normal groups, mean serum IgD level did not differ significantly on the bases of age, sex or asthmatic status. Furthermore, total serum IgD was not significantly correlated with total serum IgE (r = 0.14; P = 0.14; n = 108), indicating that immunoregulatory control of the basal levels of the two isotypes is not linked.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of protein D, an immunoglobulin D-binding protein, in Haemophilus strains

Protein D, a novel surface protein of the bacterial species Haemophilus influenzae with specific affinity for human immunoglobulin (Ig) D was detected in all 127 H. influenzae strains studied. All strains representing different serotypes of encapsulated strains and different biotypes of nonencapsulated strains bound 125I-labeled IgD to a high degree (38 to 74%). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (immunoblot) analysis showed that protein D from all H. influenzae strains had the same apparent molecular weight (i.e., 42,000) and reacted with all three different anti-protein D monoclonal antibodies. By Scatchard analysis, the number of protein D residues on a nontypeable H. influenzae strain was estimated to be approximately 2,800 per organism. The equilibrium constant for the reaction between a human IgD myeloma protein and IgD was found to be 5.8 x 10(8) M-1. Also, all strains of H. haemolyticus and H. aegypticus strains tested bound IgD, 21 to 28% and 41 to 48%, respectively. In extracts of those bacteria, a 42,000-molecular-weight protein reactive with IgD and all three anti-protein D monoclonal antibodies was found. In H. parainfluenzae, H. aphrophilus, H. paraphrophilus, and Actinobacillus actinomycetemcomitans, a 42,000-molecular-weight protein that was reactive with one to three of three anti-protein D monoclonal antibodies but not reactive with human IgD was detected with Western blot analysis. Other Haemophilus species (H. ducreyi, H. parasuis, H. parahaemolyticus, H. segnis, and H. haemoglobinophilus) did not react with human monoclonal IgD or anti-protein D antibodies. On the basis of the wide distribution of protein D among H. influenzae strains, we suggest that protein D could be a vaccine candidate.

Gammapathies monoclonales en Tunisie

Protein electrophoresis and immunoelectrophoresis carried out on 4805 sera and 93 urine samples from Tunisian patients over 8 years, and a monoclonal protein was detected in 198 cases. The distribution of the monoclonal compounds to the clinical diagnosis was studied. 115 (58%) were classified as multiple myeloma (MK), 34 (17%) as alpha heavy chain disease (MCL a), 34 (17%) as monoclonal gammapathy associated to various diseases (GMOD), 11 (6%) as benign essential monoclonal gammapathies (GMBE), 4 (2%) as Waldenström's macroglobulinemia (MW). The relationship between the monoclonal immunoglobulin and the clinical diagnosis, the distribution of the monoclonal compounds according to the heavy chain class and the identification of the light chains were studied. The results obtained are in line with the principal data in literature concerning monoclonal gammapathy. However there is a particularity about monoclonal gammapathy observed in the Tunisian's population studied: Higher percentage of alpha heavy chain diseases, monoclonal IgD and monoclonal light chain. Lower percentage of monoclonal IgM in GMBE or GMOD, as in MW.

Is IgD Myeloma a Separate Clinical Entity? Report of Six Cases Investigated by Isoelectric Focusing.

Six IgD myeloma patients whose monoclonal components were identified by isoelectric focusing are presented. They represented 4% of all patients with myeloma seen at our institute between 1982 and 1986. The patients did not display many of the features described as typical for IgD myeloma: in particular younger age group, decreased survival and increased incidence of lymphadenopathy, hepatosplenomegaly, extraosseous disease, anemia, renal failure and hypercalcemia. However males predominated, the concentrations of circulating monoclonal IgD were low and concentrations of serum and urinary monoclonal free light chains were high, findings previously reported in IgD myeloma. The concentrations of circulating IgD were at the lower end of ranges reported previously. The hypothesis that our patients represent the malignant equivalent of the normal "low secretory phenotype", possibly associated with improved survival, is discussed. The belief that IgD myeloma is a separate clinical entity is questioned. The sensitive, high-resolution technique of isoelectric focusing is recommended as the investigation of choice for the detection of monoclonal gammopathies in body fluids.

Induction and properties of syngeneic murine anti-immunoglobulin D.

High titers of autoantibodies directed to isotypic determinants of IgD were produced by inoculation of syngeneic monoclonal IgD, conjugated covalently to keyhole limpet hemocyanin, into adult or neonatal inbred mice. Anti-idiotypic antibodies were induced at the same time. The average affinity of the mouse antibodies (Ka approximately equal to 10(7) M-1) is similar to that of rabbit anti-IgD and of syngeneic anti-IgE induced by the same procedure. Results indicate that B cells of the mice are not tolerant to serum IgD and that tolerance is maintained at the level of T cells. Direct interaction of the syngeneic anti-IgD with cell-surface IgD was minimal, and there was no convincing evidence that cell-surface IgD was down-regulated in the anti-IgD-producing mice. Further studies, preferably employing monoclonal anti-IgD, are required to determine whether epitopes on cell-surface IgD can be recognized by syngeneic anti-IgD. The ability to generate in vivo high titers of anti-IgD should facilitate the production of such monoclonal antibodies.

Human IgD and IgA1 compete for D-galactose-related binding sites on the lectin jacalin.

Lectin selectivity for human Ig classes is based on carbohydrate differences. Earlier reports that the lectin jacalin precipitated human IgA were confirmed and supplemented by the current study, which demonstrates that jacalin also binds human IgD as evaluated by micro-ELISA and SDS-PAGE. Experimental findings indicated that: (i) Monoclonal and polyclonal (sera) IgD, IgA1, but not IgA2, IgM, or IgG1-4 reacted with jacalin. (ii) Six tested monoclonal IgD proteins each bound approximately equally to jacalin when antigenicity rather than protein concentration was measured: the results weigh against the presence of jacalin-detectable IgD subclasses or genetic variants. (iii) IgD and IgA1 both associated maximally in 4-8 h at 4 degrees C. There was no dissociation at 4 degrees C but limited dissociation occurred at 37 degrees C after 24 h. (iv) Both IgD and IgA1 were eluted from jacalin by galactose-related sugars. (v) IgD and IgA1 bind competitively to jacalin. The results suggested that jacalin reacts with O-linked oligosaccharide N-acetyl-galactosamine (GalN) residues found on the hinge region of both IgD and IgA1. Jacalin also interacted with one major and several minor unidentified sera proteins. The findings offer an approach to the isolation of serum polyclonal IgD and to the characterization of the unusual carbohydrates of the human delta heavy chain with respect to their function.

In vitro studies on human IgD. II. IgD-secreting cells preferentially elaborate IgD, lambda molecules.

The "IgD paradox" describes the unexpected finding that, despite a predominance of kappa (kappa) light (L) chains on the surface of IgD+ human B cells, the majority of monoclonal IgD proteins are of lambda (lambda) type. This potentially informative phenomenon appears to be based on a preferential association between delta (delta) heavy (H) and lambda L chains of IgD-secreting cells. The current studies analyze the phenomenon in vitro. Initial assays on tonsil "spent" supernatants showed that the higher IgD-"externalizing" cultures displayed progressively elevated IgD, lambda/kappa ratios due to parallel shifts in total IgD and IgD, lambda while IgD, kappa remained stable. The cells of the same higher-IgD cultures demonstrated that individual IgD-containing cells had a predominance of lambda chains in contrast to IgM-containing cells of the same cultures using fluorochrome-antibody double staining. Certain tonsil culture IgD-containing cells remarkably appeared to have exclusively lambda chain. These same tonsils show evidence of IgD secretion (Litwin, S. D. and Zehr, B. D., Eur. J. Immunol. 1987. 17:483); thus, these data align preferential delta-lambda chain association with IgD-secreting normal tonsil B cells in vitro and emphasize the usefulness of IgD, lambda/kappa ratio in monitoring IgD secretion. In another approach the relationship between the cellular location of IgD and the preferential delta-lambda chain association was studied using Triton X-114-partitioned cell lysates. IgD, lambda/kappa ratios were one or less in the detergent phase (membrane-enriched fraction) consistent with expected IgD, kappa predominance in membrane IgD. In contrast, the aqueous phase (intracellular-enriched fraction) of IgD-secreting cultures had 2-4 times higher supernatant IgD, lambda/kappa ratios. The restriction of high IgD, lambda/kappa ratios to intracellular fractions and supernatants of IgD-secreting cultured cells parallels the predicted distribution of secretory IgD. In sera studies, the correlation between total IgD and IgD, lambda/kappa ratio values was consistent with secreted sera IgD showing preferential lambda chain expression. It was concluded that the phenomenon of delta-lambda chain preferential association is expressed in vitro as well as in vivo; a property of normal, nonmalignant human IgD-secreting B cells; and closely related to the secretory form of IgD. In certain cultures, the delta-lambda chain preference was so striking as to imply limited heterogeneity of the IgD immune response.

Interaction between human IgD and ricinus agglutinin.

The results show that monoclonal IgD reacts specifically with ricinus agglutinin (molecular weight 120,000) (RcAI). The reaction between IgD and RcAI was inhibited by galactose and lactose but not by glucose, indicating that the interaction is mediated by galactose containing carbohydrate units located in or near the sigma-hinge region. Affinity chromatography on RcAI-Sepharose 4B was successfully used to isolate monoclonal IgD from the IgD myeloma plasma.