Cells Of Lymphoid Origin Research Articles

C1qRP, the C1q Receptor That Enhances Phagocytosis, Is Detected Specifically in Human Cells of Myeloid Lineage, Endothelial Cells, and Platelets

The complement component C1q can interact with a variety of different cells, resulting in multiple functional consequences depending on the cell type. mAbs R3 and R139, which recognize a 126,000 Mr (reduced) cell surface protein, are able to abrogate the C1q-mediated enhancement of monocyte phagocytosis. The cDNA encoding this C1q receptor that modulates phagocytosis, C1qRP, has recently been cloned. Using a DNA probe based on the coding region of the receptor, Northern blot and RT-PCR analysis of RNA isolated from different cell types showed C1qRP expression in cells of myeloid origin and in endothelial cells, but not in cells of lymphoid origin nor in the HeLa epithelial-like cell line or iliac artery smooth muscle cells. FACS analysis of cell surface expression of C1qRP, as detected by mAb R139 and R3, corresponded in all cases to the mRNA levels detected. Using the anti-C1qRP mAb, the 126,000 Mr receptor was also detected in lysates of human platelets. Interestingly, C1qRP is not expressed by the promyelocytic leukemia cell line HL-60, and differentiation of these cells with various chemical compounds did not induce C1qRP expression. It has been reported that C1q can induce specific receptor-mediated responses in fibroblasts. However, RNA and cell surface expression analysis for C1qRP indicate that this particular C1q receptor is not expressed by either human gingival or human skin fibroblasts. These data demonstrate selective expression of C1qRP in specific cell types and support the hypothesis that there is more than one C1q receptor mediating the diverse responses triggered by C1q.

CLASSICAL HODGKIN AND REED-STERNBERG CELLS DEMONSTRATE A NON-CLONAL IMMATURE B LYMPHOID LINEAGE: EVIDENCE FROM A SINGLE CELL ASSAY ANDIN SITU HYBRIDIZATION

Hodgkin and Reed-Sternberg (H & RS) cells are generally considered to be the neoplastic cells of Hodgkin's disease (HD), however such cells are only found in a minority of the lesions. Recently in a few studies on HD, the clonality of H & RS cells was examined, using a single-cell polymerase chain reaction (PCR) examination. To clarify the lineage and clonality of H & RS cells, we performed single cell PCR and in situ hybridization (ISH), and nine cases of classical HD were thus studied. By ISH, the immunoglobulin J chain, and the kappa and lambda light chain were rarely expressed in the H & RS cells, however, no T-cell markers could be detected. The expression of the recombination activating genes (RAG-1, 2) could be determined in the H & RS cells. We isolated CD30+ H & RS cells, CD3 + T cells and CD20 + B cells from suspended materials using a mechanical sorter. We performed single cell PCR in a sorted individual cell, to amplify the complementarity determining region of the Ig heavy chain (IgH) gene and T-cell receptor gamma chain (TCR gamma) gene. In all cases, TCR gamma could be frequently amplified in the T cells, but was only rarely amplified in the H & RS and B cells. In contrast, the IgH was frequently amplified in the H & RS and B cells, but not in the T cells. In addition, the PCR production of the H & RS cells all showed different lengths. The results therefore support the polyclonal nature and immature B lymphoid cell origin of H & RS cells.

Human papillomaviruses (HPV) are associated with multiple myeloma

Human papillomaviruses (HPV) are small DNA tumor viruses, and are associated with epithelial neoplasias. Although HPV are believed to be exclusively permissive in terminally differentiated squamous cells, we have previously identified HPV sequences in lymphoid tissues of five patients. Because this result suggested that the range of the host virus cells could include cells of lymphoid origin, we used PCR and in situ hybridization to analyze nonepithelial tissues of patients with multiple myeloma from two institutions. A statistically significant association was established between HPV and multiple myeloma (p<0.001). This study supports the hypothesis that HPV can infect lymphoid cells.

Antiviral activity and protection of cells against human immunodeficiency virus type-1 using an antisense oligodeoxyribonucleotide phosphorothioate complementary to the 5′-LTR region of the viral genome

A COS-like monkey kidney cell line stably transfected with the plasmids pCMV gagpol-rre-r with the gag and pol genes, and pCMV rev with the rev gene of HIV-1 derived from the cDNA clone BH10, was used as a model for assessing the effectiveness of antisense (AS) constructs. A 20-mer oligodeoxyribonucleotide (oligo) phosphorothioate sequence (5'-CCG CCC CTC GCC TCT TGC CG) complementary to a portion of the 5'-long terminal repeat (5′-LTR) of the HIV-1 genome was tested for its inhibitory effects on the biologically important processes of HIV-1 replication and proliferation. We observed a concentration-dependent inhibition of HIV protein synthesis. Desitometric analysis of data from Western blot analysis showed sequence-specific and concentration-dependent oligo inhibition of p24 viral core antigen formation in the low-μM range. When lipofectin was used as a delivery vehicle, a markedly increased potentiation of the AS activity of the sequence was observed at a lower concentration (0.1 μM), following a 24-h preincubation. The AS construct specifically inhibited intracellular p24 production in chronically HIV-1-infected cells of lymphoid origin (H9/IIIB cells) by 95%, resulting in a 15-fold inhibitory effect relative to a similar sequence thiolated at only seven single-base positions. A concentration-dependent attenuation in the reverse transcriptase activity and a reduction in viral p24 level was observed in the culture supernatant of AS-pretreated HIV-1-infected phytohemagglutinin A-stimulated human cord blood mononuclear cells. Incubation of a HIV-1-infected lymphoid cell line with AS sequence resulted in a marked reduction in syncytium formation, and therefore protected cells from the cytopathic effects of the virus. Furthermore, the AS oligo did not appear to be cytotoxic in cell growth rate and colony-forming ability assays. The AS oligo described in this report is a useful new tool for the molecular analysis of HIV-1 gene expression and proliferation, and may have potential as a therapeutic agent.

Intrarenal extramedullary erythropoiesis in renal allograft fine-needle aspirates

Recombinant human erythropoietin (rhEPO) is widely used in patients with end-stage renal disease and occasionally in renal allograft recipients to correct anemia. Red blood cell production is markedly increased by rhEPO; however, no extramedullary erythropoiesis (EME) has been associated with this hormone. We observed intrarenal EME in five allograft fine-needle aspirates performed for reduced graft function in four patients between 3.7 and 7 weeks following transplantation. These four patients received rhEPO during dialysis and three resumed rhEPO therapy after transplantation; all four remained anemic. Donors were between 13 months and 13 years of age, with one pediatric and three adult recipients. Aspirates with apparently incidental EME contained all stages of red blood cell precursors, but these cells were not observed in corresponding peripheral blood samples. The hematopoietic cells could be readily distinguished from cells of lymphoid origin. There were no correlations between intragraft EME and aspirate or clinical diagnosis referable to renal dysfunction. Aspirates performed prior to 3.7 weeks or after 7 weeks did not demonstrate EME. These data suggest that endogenous EPO and rhEPO in anemic patients receiving pediatric renal allografts may activate red blood cell precursors in the young graft, inducing intrarenal EME. Recognition of this entity is important to distinguish it from immune activation or malignancy within the donor organ.

IL-2 stimulation of T lymphocytes induces sequential activation of mitogen-activated protein kinases and phosphorylation of p56lck at serine-59.

p56lck, a member of the src family of non-receptor protein tyrosine kinases, is expressed almost exclusively in cells of lymphoid origin. p56lck is known to associate with the T lymphocyte surface glycoproteins CD4 and CD8, and plays a critical role in both T lymphocyte development and activation. p56lck also associates with the beta-subunit of the IL-2R, and is activated when IL-2 binds to its receptor. Using primary cultures of Con A-activated normal splenic mouse T lymphocytes, we observed an IL-2-induced sequence of events involving p56lck. We saw a rapid (within 1 to 2 min) and transient increase in p56lck kinase activity, which preceded the activation of both the p42erk-2 and p44erk-1 mitogen-activated protein kinases, maximal activation of which was observed after 10 min. We also observed an IL-2-induced shift in the electrophoretic mobility of p56lck from an apparent molecular mass of 56 kDa (p56lck) to 60 kDa (p60lck), which reached a maximum at 15 min, the level of p60lck remaining constant for up to 4 h thereafter. This IL-2-induced shift correlated with the phosphorylation of serine-59 of p56lck, a site that mitogen-activated protein kinases are capable of modifying in vitro. The implications of these results for the understanding of both p56lck function and lymphoid cell receptor signaling pathways are discussed.

Exposure-response analysis of cancer mortality in a cohort of workers exposed to ethylene oxide.

The authors previously reported results from the largest cohort mortality study of ethylene oxide-exposed workers that has been conducted to date. Here they extend their previous work by quantitatively examining the relation between cancer mortality and ethylene oxide exposure. This study included workers from 13 of the 14 geographically distinct facilities that were included in the previous investigation. These facilities began regularly using ethylene oxide to sterilize medical supplies or spices sometime between 1938 and 1969. Workers were followed from first exposure through December 31, 1987. Historical exposures to ethylene oxide were estimated using a regression model. Standard life-table analysis was used to examine cancer mortality in three categories of cumulative exposure to ethylene oxide. The Cox proportional hazards model was also used to examine cumulative and other measures of ethylene oxide exposure as predictors of cancer mortality. In both the life-table analysis and the Cox model, a positive trend was observed in all lymphatic and hematopoietic cancer mortality for cumulative ethylene oxide exposure. This trend was strengthened when ethylene oxide exposures 10 years prior to death were discounted (lagged) and when the analysis was restricted to neoplasms of lymphoid cell origin. Despite limitations discussed in this paper, the authors believe that these findings provide some support for the hypothesis that exposure to ethylene oxide increases the risk of mortality from lymphatic and hematopoietic neoplasms. The authors intend to continue follow-up of this relatively young cohort, which may allow more definitive conclusions to be drawn in the future.

Phosphorylation of serine 59 of p56lck in activated T cells.

p56lck, a member of the src family of non-receptor protein tyrosine kinases, is expressed almost exclusively in cells of lymphoid origin. Recent evidence has implicated p56lck in a critical role both in T cell development and activation. A variety of T cell stimuli induce a shift in the electrophoretic mobility of p56lck from an apparent molecular mass of 56 kDa (p56lck) to 60 kDa (p60lck). This shift in electrophoretic mobility correlates with an increase in the phosphoserine content of the p60lck. We have shown that both 4 alpha-phorbol 12 beta-myristate acetate and OKT3 treatment of Jurkat cells, as well as 4 alpha-phorbol 12 beta-myristate acetate treatment of 171.CD4 and LSTRA cells, induced phosphorylation of serine-59 on p56lck in vivo, which correlated with the shift to p60lck. We also demonstrated that the same serine residue could be phosphorylated in vitro with mitogen-activated protein kinases and that this event was capable of reducing p56lck activity in vitro. Combined, these data suggest a novel pathway for the in vivo regulation of p56lck activity.

Expression of measles virus RNA in peripheral blood mononuclear cells of patients with measles, SSPE, and autoimmune diseases

In order to characterize measles virus (MV) infection in peripheral blood mononuclear cells (PBMCs), RNA was isolated from PBMCs after PHA-stimulation for 72 hr of 9 patients with acute measles, 16 patients with subacute sclerosing panencephalitis (SSPE), 13 patients with various autoimmune diseases, and 16 healthy control donors. The RNA obtained was screened for the presence of MVN (nucleocapsid) gene specific transcripts of either positive or negative orientation in a S1 nuclease protection assay. The sensitivity of this assay allowed us to detect one infected cell in 20,000 PBMCs or 0.1 to 0.05 copies of MV-specific RNA per cell. Using single-stranded DNA or RNA probes expression of MV genomic RNA of negative polarity could be detected in only one case of acute measles and one healthy control donor. Conversely, N-specific transcripts of positive polarity, indicating active transcription, could only be detected in patients with acute measles. In addition, in infected PBMCs and in a persistently MV-infected B cell line positive stranded N-specific transcripts containing leader usually present at very low frequency have been found in relatively increased amounts in comparison with transcripts lacking leader. Whereas the ratio of these RNA species during lytic infection with MV in Vero cells is about 1:50, the ratio found here ranges from 1:3 to 1:10. This altered ratio indicates a specific regulation of MV specific transcription in cells of lymphoid origin that has not been found in any other cell system analyzed.

Molecular analysis of clonality and bcr rearrangements in Philadelphia chromosome-positive acute lymphoblastic leukemia

Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) patients consistently show a rearrangement in a 5.8-kilobase length of chromosome 22, referred to as the breakpoint cluster region (bcr). In Ph1-positive acute lymphoblastic leukemia (ALL), the breakpoint in chromosome 22 is more heterogeneous and, in some instances, does not occur within this region. In such cases the cell of origin of the neoplastic clone and the relationship of the disease to CML has remained obscure. We have analyzed the bcr rearrangement in the malignant cells from three patients who presented with Ph1-positive ALL and who in cytogenetic studies had shown evidence of variable involvement of myeloid cells in the Ph1-positive clone. Rearrangements in bcr typical of most cases of CML were detected in purified granulocyte preparations from two of the ALL patients (nos. 1 and 2) and in the blasts from patient 3 at the time of her terminal relapse. In the same analysis the simultaneously obtained granulocytes from patient 3, however, did not show any evidence of bcr rearrangement. Patient 3 was also heterozygous for the BamHI polymorphism in the X- linked hypoxanthine phosphoribosyltransferase (HPRT) gene, thus permitting a different method of clonal analysis based on methylation differences in active and inactive alleles. When DNA from her granulocytes that had shown no bcr rearrangement was hybridized to an HPRT probe, a pattern typical of a polyclonal population was seen. A similar pattern was exhibited by her marrow fibroblasts. In marked contrast, her simultaneously isolated blasts showed an unambiguous monoclonal pattern. These findings demonstrate the origin of the disease in the first two patients in a cell with myelopoietic as well as lymphopoietic potential and confirm the restricted lymphoid cell origin of the neoplastic clone in the third Ph1-positive ALL patient. Furthermore, they indicate that different target cells for transformation within the hematopoietic system may be affected by very similar bcr rearrangements.

Molecular Analysis of Clonality and bcr Rearrangements in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) patients consistently show a rearrangement in a 5.8-kilobase length of chromosome 22, referred to as the breakpoint cluster region (bcr). In Ph1-positive acute lymphoblastic leukemia (ALL), the breakpoint in chromosome 22 is more heterogeneous and, in some instances, does not occur within this region. In such cases the cell of origin of the neoplastic clone and the relationship of the disease to CML has remained obscure. We have analyzed the bcr rearrangement in the malignant cells from three patients who presented with Ph1-positive ALL and who in cytogenetic studies had shown evidence of variable involvement of myeloid cells in the Ph1-positive clone. Rearrangements in bcr typical of most cases of CML were detected in purified granulocyte preparations from two of the ALL patients (nos. 1 and 2) and in the blasts from patient 3 at the time of her terminal relapse. In the same analysis the simultaneously obtained granulocytes from patient 3, however, did not show any evidence of bcr rearrangement. Patient 3 was also heterozygous for the BamHI polymorphism in the X-linked hypoxanthine phosphoribosyltransferase (HPRT) gene, thus permitting a different method of clonal analysis based on methylation differences in active and inactive alleles. When DNA from her granulocytes that had shown no bcr rearrangement was hybridized to an HPRT probe, a pattern typical of a polyclonal population was seen. A similar pattern was exhibited by her marrow fibroblasts. In marked contrast, her simultaneously isolated blasts showed an unambiguous monoclonal pattern. These findings demonstrate the origin of the disease in the first two patients in a cell with myelopoietic as well as lymphopoietic potential and confirm the restricted lymphoid cell origin of the neoplastic clone in the third Ph1-positive ALL patient. Furthermore, they indicate that different target cells for transformation within the hematopoietic system may be affected by very similar bcr rearrangements.

An innate host response to the neoplastic cell: syngeneic rat tumor cells can elicit a rapid de novo lymphoid procoagulant response.

Abstract To analyze unique molecular differences between normal and neoplastic cells, we have examined host responses to tumor cells. The present study provides the first evidence for an innate rapid recognitive response of the lymphoid system to some syngeneic tumors. The lymphoid procoagulant (PCA) response, a T cell-instructed monocyte response that activates proteases of the coagulation cascade culminating in thrombin formation, is considered a component of classic delayed-type hypersensitivity responses. We have demonstrated that three syngeneic rat mammary carcinomas elicit this cellular response in vitro in lymphoid cells of the unimmunized rat. The response was rapid, reaching maximum within 6 hr. Analysis was compounded by the constitutive PCA activity of some tumors; however, the PCA product produced in the response to tumor challenge in vitro was newly biosynthesized and was of lymphoid cell origin, differing from the PCA of tumor cells. The lymphoid PCA response was prothrombinase-like and did not require vitamin K for biosynthesis, nor were other gamma-carboxylation-dependent extrinsic pathway proteases other than prothrombin required for thrombin generation. Both in vivo and in vitro derived mammary carcinoma cells elicited the response, whereas a fibrosarcoma and nontransformed syngeneic cells did not. Tumor shed substances, which were devoid of PCA and sedimentable only in part at 100,000 X G, induced this cellular response. The same stimuli shed from tumor cells did not directly elicit a PCA response from elicited peritoneal macrophages; however, in the presence of T lymphocytes a PCA response of these macrophages was produced. This study provides novel information to indicate that a T-enriched lymphocyte-dependent monocyte-macrophage response to some tumors, before effective in vivo immunization, may participate in initial local protease generation and fibrin deposition, both thought to play a significant role in the local pathobiology of tumors.

Immune interferon induces the receptor for monomeric IgG1 on human monocytic and myeloid cells.

We report here that FcR for human monomeric IgG1 can be induced on cells of myeloid origin cultured in the presence of IFN gamma for 8 h. Supernatant fluids from cultures of lymphocytes infected with a variety of viruses or cocultured with cell lines have the same FcR enhancing effect as IFN gamma. We identify the factor in the supernatant fluid responsible for the induction as immune interferon. Among the different types of IFN, only the gamma type (both purified and recombinant) specifically induces the appearance of FcR for monomeric IgG1 on normal and leukemic myeloid cells but not on cells of lymphoid origin. This effect is also evident on mature PMN. We show that the specificity and the affinity of the receptor induced on HL-60 promyelocytic cells, peripheral blood monocytes, and PMN are identical to those of the receptor spontaneously present on the same cells, except for PMN, which do not spontaneously express this type of receptor. The results of inhibition experiments performed with mouse IgG of and IgG3. These results suggest that the receptor present on human monocytes different isotypes indicate that the receptor can be inhibited by murine IgG2a or immature myeloid cells, selectively inducible by IFN gamma, has a specificity similar to the FcR1 described on mouse macrophages.

2‘,5‘-Oligo(A)-activated endoribonuclease. Tissue distribution and characterization with a binding assay.

We have measured the binding of highly radioactive (2'-5')pppA4-5[32P]cytidine 3',5'-diphosphate to human, mouse, and rabbit cell and tissue extracts. A binding activity for this oligonucleotide is present in all extracts examined and high levels of this activity are found in some cells of lymphoid origin. In particular, the mouse thymoma cell line W7 has about 10 times higher binding activity than other cell lines. The oligonucleotide is bound with a single high affinity constant, as shown by Scatchard plot analyses. Cell extracts fractionated by centrifugation on glycerol gradients show a single peak of binding activity, which co-sediments with (2'-5')oligo(A)-dependent endoribonuclease (RNase L). This enzyme apparently binds the oligonucleotide, as shown by experiments with an analog of (2'-5')oligo(A) which competes in the binding and inhibits the RNase L. This endonuclease cannot be directly assayed in unfractionated cell or tissue extracts with high levels of other nuclease activities. The binding assay for the oligonucleotide may provide an estimate of RNase L levels in such cell and tissue extracts.

Expression of human placental cell surface antigens on peripheral blood lymphocytes and lymphoblastoid cell lines.

The expression of human placental cell surface antigens was examined in cells of lymphoid origin, including peripheral blood lymphocytes and cultured lymphoblastoid cells of bone marrow or thymus derivation. A select group of this defined set of surface antigens was detected on all three cell preparations. The most remarkable observation was the conspicuous absence of three subunits previously demonstrated to be present on all human cell surfaces examined to date. Antiserum directed against several placental components prevents adhesion and spreading of cells which grow attached to surfaces. These results suggest a role for these three glycoproteins in mediating cellular adhesion.

Synthesis of two distinct interferons by human fibroblasts

Human interferon species Le and F can be distinguished on the basis of their distinct antigenic, biological, and physicochemical characteristics. Until now, Le interferon was thought to be produced only in cells of lymphoid origin. This study demonstrates that cultures of human fibroblast cell strains GM-258 and FS-4 produce both F and Le interferons. Le interferon constituted up to about 20% of the total interferon activity produced in fibroblast cultures after stimulation with Newcastle disease virus or vesicular stomatitis virus. In contrast, only F interferon was detected in preparations obtained after induction with polyinosinate-polycytidylate. These results indicate that the Le interferon gene is inducible in cells of nonlymphoid origin and that the expression of this gene depends on the nature of the inducing agent.

Host origin of lymphoid cells in thymomas developed from subcutaneous thymus grafts in Buffalo rats.

Ten out of 31 male Buffalo rats developed thymomas, 18 months after birth, from the subcutaneous thymuses grafted neonatally either from female or male litter mates. Most of them were of lymphoid cell type and contained numerous lymphoid cells within the network composed of neoplastic epithelial cells, as mediastinal thymomas. Lymphoid cells in the subcutaneous thymomas had normal diploid karyotype and were of host type with the Y chromosomes. These facts may indicate that lymphois cells intermingled in the network of neoplastic epithelial cells are non-neoplastic in nature.

Suppression of DNA synthesis in hepatoma cells exposed to glucocorticoid hormone in vitro.

Glucocorticoid hormone is shown to markedly suppress DNA synthesis in a line of rat hepatoma cells in vitro. In the presence of 300 nM hydrocortisone or 30 nM dexamethasone the incorporation of radioactive thymidine falls to 50% of control levels by 36 hr, and at higher concentrations of hormone inhibition can be noted as early as 12 hr and is nearly complete by 24 hr. This inhibition of radioactive thymidine incorporation reflects a true suppression of DNA synthesis, is accompanied by a corresponding inhibition of cell proliferation, and is readily reversible upon subsequent removal of hormone. In contrast to previously described effects of the glucocorticoid hormones on various cells of lymphoid origin, the inhibition of DNA synthesis in these hepatoma cells is not accompanied by appreciable cell lysis or by degradation of preformed DNA, and even when [(3)H]thymidine incorporation into DNA is inhibited by 90% or more, incorporation of [(14)C]uridine into RNA proceeds with little change. These findings all parallel previous observations on the effects of glucocorticoid hormone on the livers of intact animals and suggest that studies on the mechanism of the inhibition of DNA synthesis in the present more isolated system may lead to a better understanding of the means by which these compounds inhibit liver growth in vivo. Despite the ready suppressibility of DNA synthesis in these hepatoma cells and in two other cell lines of liver origin, none of these cell lines was found to be inducible for tyrosine aminotransferase. The apparent dissociation between two "steroid-sensitive" phenomena is of interest and warrants further investigation.

On the origin of lymphoid cells in the palatine tonsil.

The origin of the lymphoid cell populations of the tonsil was studied by sublethal whole body irradiation of normal and thymectomized animals. Two clearly distinguishable cell populations appeared to be present in the tonsil: a thymus-dependent population, situated in the interfollicular areas, and another presumably bone marrow derived lymphoid cell population, localized in the follicular structures. From the experimental data obtained, it is concluded that no fundamental difference exists between the lymphoid tissue of the tonsil and that of the regional lymph nodes in the adult animal.

Origin and fate of lymphoid cells in the developing palatine tonsil of the rabbit. A possible mechanism of homing of lymphoid cells.

The origin of lymphoid cells in the developing palatine tonsil is a matter of controversy. Many authors assume an intrinsic origin by transformation of mesenchymal or epithelial cells of the tonsillar primordium, whereas some advocate an extrinsic haematogenous origin. To gain insight into this question a study was made of the morphology of the first appearing lymphoid cells in the developing palatine tonsil of the rabbit. Light- and electron-microscopic examination of the developmental stages at 24 hr intervals revealed the appearance of motile lymphoid cells in the tonsillar area on the 22nd day of gestation. On the 23rd day the motile cells were found to be in close contact with the cells of the condensed mesenchyme surrounding the primary tonsillar crypt. The contact between the motile lymphoid cells and the mesenchymal cells appears to be established by the formation of a number of close junctions. On the 24th day the lymphoid cells contacting the mesenchymal cells lose their motile features and differentiate into dense lymphoid cells. It is concluded that lymphoid cells of extrinsic origin migrate into the tonsillar primordium where they are immobilized by the cells of the condensed mesenchyme, after which they differentiate into dense lymphoid cells.