B-cell Patients Research Articles

Detection of autoreactive B-lymphocytes in patients with acute optic neuritis employing an immunospot assay

Detection of autoreactive B-lymphocytes in patients with acute optic neuritis employing an immunospot assay

Detection of autoreactive B-lymphocytes in patients with acute optic neuritis employing an immunospot assay

Detection of autoreactive B-lymphocytes in patients with acute optic neuritis employing an immunospot assay

Elevated serum interleukin-6 associated with a failur in B cell differentiation in common variable immunodeficiecy

Interleukin-6 (IL-6/B cell stimulatory factor 2) has been found to drive activated human B-lymphocytes through the final stages of differentiation to become immunoglobulin-producing cells. Most patients with common variable immunodeficiency (CVI) have B-lymphocytes that fail to differentiate into high-rate immunoglobulin-secreting cells in vivo and in vitro. In view of (1) the known effects of IL-6 to promote B-lymphocyte terminal differentiation and (2) the defect in differentiation in B-lymphocytes of patients with CVI, we believed that it was important to analyze the role of this cytokine in patients with CVI. Using an IL-6-dependent murine hybridoma cell line in a bioassay, serum IL-6 levels were determined in 17 patients with CVI and in eight normal control subjects. Thirteen of the 17 patients with CVI exhibited serum IL-6 levels that were twofold to 18-fold higher than the range (mean, +2 SD) of normal control subjects. Spontaneous IL-6 production by peripheral blood mononuclear cells (PBMC) of patients with CVI was significantly higher than that from normal control subjects, whereas lipopolysaccharide maximally stimulated IL-6 production by PBMCs of patients with CVI or PBMCs of normal control subjects was equivalent. A substance inhibitory of IL-6 bioactivity was found in equivalent amounts in sera of both patients and normal control subjects. Sera from patients with CVI with high IL-6 bioactivity were found to have saturated this IL-6 inhibitory substance, thus resulting in large amounts of free IL-6 in the sera. These studies suggest that the failure of B cells from patients with CVI to terminally differentiate into high-rate immunoglobulin-secreting cells cannot be attributed to a decrease in the serum levels of IL-6 and that the increased circulating IL-6 levels in patients with CVI result from hyperproduction rather than decreased use of IL-6. The persistently elevated levels of IL-6 observed in some patients with CVI may secondarily result in the induction of the neoplastic and autoimmune phenomena associated with this disease.

Dipeptidylaminopeptidase IV in lymphocytes of patients with lymphoproliferative diseases

DAP-IV activity (Gly-Pro-MCA hydrolysis, pH 7.8) was found in lysates of peripheral blood lymphocytes of patients with T- and B-cell forms of malignant lymphoproliferative diseases. The highest DAP-IV activity was seen in the cells of patients with a rare variant of T-cell lymphocytic leukemia (T-CLL); these cells expressed simultaneously the antigens of T helpers and T suppressors (Th and Ts) (OKT4+ and OKT8+). The DAP-IV activity about ten times less was found in the pathological cells with a phenotype of mature Th (Sezary disease), as well as in the cells expressing antigens of both Ts and natural killers (a rare variant of T-CLL). The same activity was also found in Ts (T gamma-lymphocytosis). The data obtained show that the differences in DAP-IV expression are connected with the differentiation step rather than with the belonging to a particular subpopulation of T-cells. DAP-IV activity, which was somewhat lower than that of T-cells, was found in B-lymphocytes of patients with B-CLL, hair-cellular leukemia, and non-Hodgkin's lymphoma. No correlation of DAP-IV activity with the level of E-cellular differentiation was observed.

Immunoregulatory factors controlling terminal differentiation of malignant B-lymphocytes.

B-lymphocytes of patients with chronic lymphocytic leukemia differentiate in vitro towards plasma cells upon activation with Pokeweed mitogen (PWM) and Cowan. The level of response is much lower than that of normal cells and so is the helper T-cell function. However, concanavalin A-activated suppressor T-cell function of Ig synthesis is normal. Malignant B-cells have a normal capacity to stimulate Ig synthesis in the mixed lymphocyte cultures, but they respond poorly to an allogeneic stimulus. Thymosin (TFX) causes a marked enhancement of PWM-driven differentiation of malignant B-cells.

831 WISKOTT-ALDRICH SYNDROME: IMMUNE STATUS AFTER BONE MARROW TRANSPLANTATION

An 18 month old boy with Wiskott-Aldrich Syndrome (WAS) received a marrow transplant from an HLA-matched sister after being conditioned with cyclophosphamide and dimethyl-myleran; post transplant methotrexate was given for 6 weeks. Complete hematologic reconstitution with donor cells occurred. In vitro immunoglobulin (Ig) synthesis was determined with a direct and an indirect hemolytic plaque assay using pokeweed mitogen activation and co-culture techniques. Before transplantation, Ig secretion of B cells was impaired; T-cells provided adequate help and suppressor T-cells were not detected. Following transplantation, a transient impairment of IgG secretion by patient's B-cells in the presence of autologous or normal allogeneic T-cells was observed. During three months of post-transplant study, T-helper activity was persistently defective and Ig secretion by normal B and T cells was suppressed (> 95%) by the patient's T cells. Recovery from the transplant procedure was rapid and 3 months after the transplant the patient was infection-free and without signs of graft versus host disease; serum immunoglobulin concentrations were normal and isohemagglutinins became demonstrable; he responded to bacteriophage OX 174 with adequate antibody titers and in vitro lymphocyte transformation to mitogens was 16-51% of normal. Presently, eight months after the transplant, he is asymptomatic and thriving. These observations indicate that hematologic and immunologic reconstitution can be achieved in WAS without total body irradiation prior to marrow infusion, and that the appearance of donor derived suppressor T cells may play a role in the homeostasis between the host and graft.

Clinical and immunologic observations in a patient with late onset immunodeficiency

The case of a patient with common variable immunodeficiency and duodenal nodular lymphoid hyperplasia, suffering from diarrhea and abdominal pain, is presented. Immunoglobulins could not be detected or were very low in serum, tissues, and external secretions. Serum antibody production and delayed-type immunity were disturbed, but T-killer and K-cell function were normal. Cultured with pokeweek mitogen, the patient's B-cells failed to synthesize cytoplasmic immunoglobulin when patient T-cells were present in the medium but not when normal T-cells were added. In addition, patient T-cells suppressed Ig production by control B-cells, which suggests that the patient T-cell population was primarily responsible for the observed abnormal B-cell function. As shown by positive reaction with a specific antihuman T-cell antiserum, the lymphoid cells in the lymphoid nodules in the gut wall consisted to a large extent of T-lymphocytes. Treatment with metronidazole for giardiasis, gammaglobulin, antibiotics, and antidiarrheals was without benefit. As a terminal event, the patient developed extensive ulcerative destruction of the distal small bowel associated with evidence of widespread cytomegalovirus infection. The CMV-cells were especially numerous in the severely ulcerated small bowel. It seems highly probable that the CMV-infection contributed to the symptom complex of intractable abdominal pain, diarrhea, protein loss, and malabsorption.

T- and B-lymphocytes in patients with chronic renal failure and recipients of an allografted cadaveric kidney in the period immediately after transplantation

In frogs with epileptogenic focus induced by injection of penicillin (1000 U in 0.4 microliter) into the primordial hippocampus it was shown that pretreatment with two kynurenines (quinolinic acid -- 0.1 microgram, and d,l-kynurenine -- 1 microgram) into the focus region and their injection into the functioning epileptogenic focus led to a sharp increase of the interparoxysmal epileptiform discharges and electrographic correlates of the fit on the EEG. Anthranilic acid (5 microgram) did not influence the activity of epileptogenic foci, and serotonin (1 microgram) and 5-methoxytryptamine (1 microgram) decreased it significantly. It is suggested that the effect of kynurenines on neurones in the epileptogenic foci may play a certain role in the pathogenesis of epilepsy.

The nature of the atypical lymphocyte in infectious mononucleosis

The nature of the circulating atypical lymphocytes in infectious mononucleosis (I.M.) has been examined by a battery of techniques in order to determine whether they are of bone marrow (B-lymphocyte) or thymic (T-lymphocyte) origin. To identify T-lymphocytes, the spontaneous sheep erythrocyte rosette technique was used; to identify B-lymphocytes, a rosette method using sheep erythrocytes coated with pure anti-human F(ab') 2 was employed. These methods were used in combination with tritiated thymidine incorporation and radioautography to identify the dividing B- or T-lymphocytes. The results obtained indicate that there is a 6.2-fold increase in circulating T-lymphocytes and a 5.3-fold increase in B-lymphocytes in patients with I.M. as compared to normal controls. The percentage of tritiated thymidine labeled mononuclear cells was less than 0.2% in five normal controls while it ranged from 4.8 to 9.4% (mean 6.6%) in five I.M. patients. There was a marked increase in the number of labeled circulating T- and B-lymphocytes to 313/mm 3 (normal < 1.5/mm 3) and 136/mm 3 (normal < 1/mm 3), respectively. These results demonstrate that both the T- and B-lymphocytes are part of the atypical lymphocyte population and are stimulated to divide in I.M.

Studies of T- and B-Lymphocytes in Patients With Connective Tissue Diseases

Studies of T- and B-Lymphocytes in Patients With Connective Tissue Diseases

Peripheral blood T- and B-lymphocytes in patients with lymphoma and acute leukemia

Peripheral blood lymphocytes from 38 patients with malignant lymphoma and 14 subjects with acute lymphatic leukemia were studied for relative distribution of thymus-derived (T-cells) and bone-marrow derived (B-cells). B-cells were identified using direct immunofluorescent enumeration of lymphocytes showing surface Ig, and T-cells were counted using indirect immunofluorescence and rabbit antihuman fetal thymocyte antisera. When absorbed with B-cells from patients with chronic lymphatic leukemia, the latter antisera appeared to show θ-like or T-cell specificity. Patients with lymphoma showed a significant increase (P < 0.01) in B-cells with surface IgG as compared with normal controls; no significant change in peripheral blood T-cell percentages among lymphoma patients was recorded using the immunofluorescent technique. By contrast acute lymphatic leukemia was characterized by a significant increase in peripheral blood T-cells (P < 0.001), and a decrease in B-cells bearing γA and γM. In several untreated acute leukemic patients the leukemic cells appeared to stain as T-cells in the assay system. Thus, chronic lymphatic leukemia is a B-cell disease and acute lymphatic leukemia affects T-cells.

Studies of T- and B-lymphocytes in patients with connective tissue diseases.

Peripheral blood lymphocytes from normal subjects as well as patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and active tuberculosis were studied for the relative distribution of bone marrow-derived lymphocytes (B-cells) and thymic-derived T-cells. B-cells were identified by direct immunofluorescence of surface Ig markers; T-cells were studied using rabbit antisera to pooled human fetal thymocytes absorbed with chronic lymphatic leukemia lymphocytes as a source of B-cells. In normal subjects, the sum of percentages of peripheral blood lymphocytes staining for surface Ig (B-cells) plus the percentage of cells staining with the absorbed antithymocyte antiserum closely approximated 100%. The mean value for percent B-cells among 51 normals tested was 22.9%+/-7.1; mean T-cells value was 75.3+/-13.95%. T-cell-specific antiserum stained 18% of normal human bone marrow lymphocytes, 42.5% of lymphocytes from normal spleens, and 98% of cells obtained from thoracic duct drainage of patients with RA. Specificity of antihuman thymocyte antiserum appeared to depend on the use of living cells. When patients with RA were examined, a wide range (14-98%) of peripheral blood T-cell values was found. Values for low percentages of peripheral blood T-cells appeared to correlate to some extent with severe clinical disease. In 11 of 36 RA patients, the sum of identifiable B- plus T-cells accounted for only 34-55% of peripheral blood lymphocytes. The identity of the remaining "null" cells could not be identified.3 of 24 SLE patients studied showed low percentages of peripheral blood T-cells, but no correlation could be drawn between T- to B-cell ratios and clinical disease activity. Among 21 patients with active tuberculosis, one had a low value for identifiable T-cells. No significant differences from normals in range or proportion of B-cells was identified in patients with active tuberculous infection.