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Results for “Extrafollicular differentiation”

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At least 19 recordsLinked to original sources

PubMed1997

Viral superantigen drives extrafollicular and follicular B cell differentiation leading to virus-specific antibody production.

Mouse mammary tumor virus (MMTV[SW]) encodes a superantigen expressed by infected B cells. It evokes an antibody response specific for viral envelope protein, indicating selective activation of antigen-specific B cells. The response to MMTV(SW) in draining lymph nodes was compared with the response to haptenated chicken gamma globulin (NP-CGG) using flow cytometry and immunohistology. T cell priming occurs in both responses, with T cells proliferating in association with interdigitating dendritic cells in the T zone. T cell proliferation continues in the presence of B cells in the outer T zone, and B blasts then undergo exponential growth and differentiation into plasma cells in the medullary cords. Germinal centers develop in both responses, but those induced by MMTV(SW) appear later and are smaller. Most T cells activated in the T zone and germinal centers in the MMTV(SW) response are superantigen specific and these persist for weeks in lymph nodes draining the site MMTV(SW) injection: this contrasts with the selective loss of superantigen-specific T cells from other secondary lymphoid tissues. The results indicate that this viral superantigen, when expressed by professional antigen-presenting cells, drives extrafollicular and follicular B cell differentiation leading to virus-specific antibody production.

Animals↗

PubMed1999

B cell response after MMTV infection: extrafollicular plasmablasts represent the main infected population and can transmit viral infection.

The immune response to mouse mammary tumor virus (MMTV) relies on the presentation of an MMTV-encoded superantigen by infected B cells to superantigen-specific T cells. The initial extrafollicular B cell differentiation involved the generation of B cells expressing low levels of B220. These B220low B cells corresponded to plasmablasts that expressed high levels of CD43 and syndecan-1 and were CD62 ligand- and IgD-. Viral DNA was detected nearly exclusively in these B220low B cells by PCR, and retroviral type-A particles were observed in their cytoplasm by electron microscopy. An MMTV transmission to the offspring was also achieved after transfer of B220low CD62 ligand- CD43+ plasmablasts into noninfected females. These data suggest that B220low plasmablasts, representing the bulk of infected B cells, are capable of sustaining viral replication and may be involved in the transmission of MMTV.

Animals↗

PubMed1996

The production of immunoregulatory cytokines is localized to the extrafollicular area of human tonsils.

The localization and production at the single cell level of 19 different human cytokines, IL-1 alpha, IL-1 beta, IL-1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, TNF alpha, TNF beta, IFN gamma, GM-CSF, G-CSF, and TGF beta 1-3, were studied in cryopreserved tonsillar tissue using immunohistochemical staining. The cytokine producing cells, with the exception of IL-1 expressing cells, had a characteristic morphology due to the accumulation of cytokine onto the Golgi organelle. The production of each cytokine was localized to specific compartments in tonsillar tissue sections from children with tonsillar hypertrophy or recurrent tonsillitis in the resting state. Immunoregulatory cytokines such as IL-2, IL-3, IL-4, G-CSF, GM-CSF and TGF beta were produced in the extrafollicular area and entrapped on the cell membranes as well as in pudels in the extracellular matrix surrounding the producer cells. The dominating cytokines both in tissues from recurrent tonsillitis and tonsillar hypertrophy were GM-CSF, G-CSF, and TGF beta 1-3 which were synthezised predominantly in the reticular crypt site. IL-1 alpha, beta and IL-1ra, on the other hand, were localized to the surface and crypt epithelium and to scattered regions in the extrafollicular area. IL-2, IL-6, IFN gamma and IL-10 were found much more often in sections obtained from recurrent tonsillitis tissue compared with those from tonsillar hypertrophy. Reversely, an excessive production of IL-4 was noted in tonsillar hypertrophy compared with that in recurrent tonsillitis. Thus, concomitant production of multiple cytokines was evident with similarities but also differences in cytokine pattern between the two groups studied. The data suggest that T-cell mediated B-cell activation and differentiation take place in the extrafollicular area. Children with recurrent tonsillitis had a higher amount of B-cells and monocytes compared with children with tonsillar hypertrophy. However, the number of CD3, CD4, CD8 or cytoplasmic Ig-positive cells did not differ between the two groups.

Cell Movement↗

PubMed1997

The changing preference of T and B cells for partners as T-dependent antibody responses develop.

Recirculating virgin CD4+ T cells spend their life migrating between the T zones of secondary lymphoid tissues where they screen the surface of interdigitating dendritic cells. T-cell priming starts when processed peptides or superantigen associated with class II MHC molecules are recognised. Those primed T cells that remain within the lymphoid tissue move to the outer T zone, where they interact with B cells that have taken up and processed antigen. Cognate interaction between these cells initiates immunoglobulin (Ig) class switch-recombination and proliferation of both B and T cells; much of this growth occurs outside the T zones B cells migrate to follicles, where they form germinal centres, and to extrafollicular sites of B-cell growth, where they differentiate into mainly short-lived plasma cells. T cells do not move to the extrafollicular foci, but to the follicles; there they proliferate and are subsequently involved in the selection of B cells that have mutated their Ig variable-region genes. During primary antibody responses T-cell proliferation in follicles produces many times the peak number of T cells found in that site: a substantial proportion of the CD4+ memory T-cell pool may originate from growth in follicles.

Animals↗

PubMedDate not supplied

[Correlations between the functional activity and proliferation of the thyroid parenchyma. The proliferative forms of the parenchyma of the thyroid].

Multiple thyroid adenomas formed by straight or coiled epithelial cords developed in experiments on adult male rats as a result of prolonged intermittent 6-MTU administration. Such epithelial cords could be sometimes observed in thyroid parenchyma regeneration after partial thyroidectomy. These cords originated from thyrocytes of the follicle epithelium. In the proliferating thyroid parenchyma DNA replication mainly terminated in endomitoses (previously reported data) which in thyrocytes of prismatic form resulted in their separation from proximal and distal daughter cells. Proximal daughter cells kept contact with the follicle lumen but distal ones lost it, hence their iodine uptake and origination weakened. Therefore, the biosynthesis of thyroglobulin decreased in cytoplasm of distal daughter cells but the formation of thyroalbumin increased. In consequence the distal daughter cells with this shift in protein biosynthesis underwent hypertrophy and further originated the proliferation of extra follicular epithelial cords. The formation of new follicles mainly took place with the differentiation of interfollicular islets separated from proliferating extrafollicular epithelial cords. Thyrotropin, the principal stimulator of hormonopoietic thyrocyte activity, did not necessarily influence the activation of thyroid parenchyma proliferative processes.

Animals↗

PubMed1993

Immunohistochemical detection of co-localizing cytokine and antibody producing cells in the extrafollicular area of human palatine tonsils.

In vitro experiments have documented the role of cytokines in the regulation of the human humoral immune response. Which cytokines are operative in vivo and in which lymphoid compartment interactions between cytokine-producing T cells and antibody-forming B cells occur is still unclear. For that reason we studied human tonsils using immunohistochemical techniques. In tissue sections from tonsils in a resting stage after recurrent tonsillitis we observed cells producing IL-1 alpha and tumour necrosis factor-alpha (TNF-alpha) which were exclusively localized in the mantle zone of the follicle and in the extrafollicular area. Furthermore, a high frequency of interferon-gamma (IFN-gamma)-producing cells was detected in the extrafollicular area, but not inside the follicles. Occasional IL-2- and IL-4-producing cells were found in the extrafollicular area. Immunohistochemical detection of antibody isotypes revealed that B cells, IgM-membrane-positive, were localized inside the follicles and mantle zones, whereas IgD-membrane-positive cells were mainly found in the mantle zones of secondary follicles. In contrast, plasma cells producing IgG1-4 and IgA1-2 were found in the extrafollicular area. No IgD and IgE antibody-forming cells were detected in tonsils, whereas IgM antibody-forming cells were detected in the extrafollicular area. The co-localization of cytokine-producing cells and antibody-forming cells in human tonsil suggests that T-B cell interactions, required for B cell differentiation and isotype switching, take place in the extrafollicular area.

Antibody-Producing Cells↗

PubMed2026

Multimodal computational framework resolves B cell maturation in autoimmunity and ageing.

Identification of the origin of pathogenic immune cells is crucial for therapeutic interventions and diagnosis but pseudotime methods struggle to trace immune cells accurately. Current trajectory inference methods for B cell development and response in health and disease either ignore or underutilize antigen receptor sequence information, limiting their ability to resolve developmental pathways, particularly for pathogenic populations. Widely used methods such as Monocle 3 reconstruct developmental paths from transcriptomic similarity alone, discarding the features from immune receptors. Dandelion has combined the immune receptor features with transcriptomics but it struggles to simulate the trajectory path of B cells. Here we present ClonoTrace, a computational framework that integrates BCR sequence features with transcriptomic trajectory inference through gated fusion of multimodal embeddings. In fetal B cell development and germinal centre development, ClonoTrace demonstrates closer concordance with the canonical reference ordering than Monocle 3 and Dandelion. Applied to systemic lupus erythematosus, ClonoTrace indicates a memory B cell extrafollicular maturation route alongside the naïve B cell route, accompanied by induction of ZEB2 with a concomitant decline of BACH2 along the trajectory, as a candidate alternative route to pathogenic double negative 2 B cells (DN2) in systemic lupus erythematosus (SLE) patients. In healthy ageing, ClonoTrace resolved three candidate age-related B cell maturation routes, from naïve, IgM+ memory and switched-memory B cells, each passing through a DN2-associated transcriptional state that is ordered before age-associated B cells along the inferred trajectory. ClonoTrace's fate probability algorithm indicated that IgM+ memory B cell to ABC transition as the leading candidate age-associated transition, which may be distinct from SLE DN2 maturation. ClonoTrace provides a generalizable framework for receptor-informed trajectory inference, describing candidate developmental routes of pathogenic B cell populations in autoimmunity and ageing.

Humans↗

PubMed1995

Immunohistochemical comparative investigations of lymphatic tissue in reactive processes, myasthenic thymuses and Hodgkin's disease.

In this study coexpression of cytokeratin and desmin, and occasionally also Ki-1 antigen, was displayed in extrafollicular reticulum cells of reactive lymph nodes. The absence or expression of trace amounts of these proteins in normal lymphoid tissue suggests that activation of T cell regions is correlated with the increased frequency of cytokeratin, desmin and Ki-1 expressing cells, and therefore may be a transient phenomenon. S-100-positive interdigitating reticular cells were found occasionally in extrafollicular T cell region of normal lymph nodes. They were, however, more numerous in reactive lymphatic tissue. In the myasthenic thymuses cells forming Hassall's corpuscles displayed coexpression of cytokeratin, desmin and Ki-1 antigen. Medullary epithelial cells were also cytokeratin-positive and, additionally, Ki-1 antigen was expressed on some cells dispersed in whole thymic tissue. S-100-positive interdigitating reticular cells were especially numerous in the thymic medulla and some of them found inside the Hassall's corpuscles. In Hodgkin's disease deficiency of cytokeratin and desmin in extrafollicular reticulum cells is a constant phenomenon in spite of a classic inflammatory background. However, Ki-1 antigen displayed Reed-Sternberg cells which, similar as some thymic cell elements, appear to originate from stromal perivascular mesenchyme. This fact suggests that Reed-Sternberg cells in Hodgkin's disease are pathologic counterparts of extrafollicular reticulum cells which represent a cellular differentiation defect to produce desmin and cytokeratin but with a possibility of Ki-1 antigen expression. The consequence of this may be the disregulation of immune system and the observed immunologic abnormalities. Further studies are needed to elucidate the role of Epstein-Barr viruses in this process. S-100-positive interdigitating reticular cells were in close contact with Reed-Sternberg cells and they were especially large and with numerous cells processes in the mixed cellularity (MC) subtype. The occurrence of interdigitating reticulum cells with S-100 protein expression, especially numerous in the T cell region activated of peripheral lymphatic tissue, as well as their close contact with Reed-Sternberg cells and with cells forming Hassall's corpuscles suggest their eventual possible role in the function of the immune system.

Adolescent↗

PubMed1981

Immunohistochemical evaluation of J-chain expression by intra- and extra-follicular immunoglobulin-producing human tonsillar cells.

Cytoplasmic J-chain expression by Ig-producing cells was characterized immunohistochemically in normal specimens of palatine and nasopharyngeal tonsils (adenoids). Altogether follicular immunocytes, which were mainly of ther IgG and IgM isotypes, showed a much higher percentage of J-chain positivity than the extrafollicular ones, in agreement with the idea that this polypeptide is principally a marker of differentiating or newly differentiated Ig-producing cells. Thus, in concurrence with the predominating IgG isotype, J-chain expression was almost 50% in the germinal centres of lymphoid follicles but only about 2% in the extrafollicular compartment. By contrast, a substantial number of J-chain-positive IgA immunocytes were found in the latter compartment. Since it is believed that extrafollicular Ig-producing cells are mainly derived from follicular centre cells, this result indicated that significant isotype switching is involved in tonsillar B-cell differentiation. Most tonsillar IgD immunocytes were J-chain-positive, in accordance with the notion that IgD expression is a feature of relatively early clonal development. It is postulated that J-chain-positive B-cell blasts may leave the tonsils and, through isotype switching, contribute to the dimer-producing IgA-cell populations normally found in the exocrine glands of the upper aero-digestive tract.

B-Lymphocytes↗

PubMed1981

Tridimensional study of the deep cortex of the rat lymph node. IV. Differential labelling of the deep cortex units with 3H-uridine.

Using tridimensional reconstruction, it was recently found that the deep cortex of rat lymph nodes comprises one to several basic "units." Each unit is a semi-rounded structure contiguous to the peripheral cortex and bulging into the medulla of a node. Other investigators reported that transfused lymphocytes, heavily labelled in vitro by 3H-uridine, became concentrated in an ill-defined region of nodes, referred to as the mid and deep cortex. This suggested to us that the in vivo labelling of nodes with 3H-uridine might allow to further characterize the units on a physiological basis. Therefore, rats were injected intravenously with a dose of 1--20 muCi of 3H-uridine/gm body weight and sacrificed 1 hour to 3 days later. The radioautographs of their nodes were exposed up to 535 days. The observations revealed that a large dose of 3H-uridine combined with a long exposure of the radioautographs yielded a differential labelling of the cell population of the units, characterized by a much more intense reaction than that of the surrounding structures. This demonstrated that the physiology of the lymphocyte population of the deep cortex units differs from the morphologically similar lymphocyte population of the extrafollicular zone of the peripheral cortex. The possible reason(s) for the differential labelling of the units is discussed.

Animals↗

PubMed1995

[In vitro differenciation and functions of dendritic cells obtained from CD34+ hematopoietic progenitors].

Dendritic Cells (DC) are professional antigen presenting cells, necessary during the initiation of immune responses. The study of the role of DC in the establishment of this response has long been tempered by the difficulties to purify DC in sufficient numbers. In vitro generation of DC, from CD34+ hematopoietic progenitors in human and mice, should permit to clarify the relationships between the different DC types isolated in vivo and their roles. GM-CSF has been described to play a key role in the propagation of DC. In human, in association with TNF alpha, it allows the generation of DC from CD34+ progenitors. Those in vitro generated DC are capable of receptor mediated endocytosis and can present soluble antigen to specific T cell clones and activate naive T cells. During activation of naive T cells CD86 (on DC)--CD28 (on T lymphocyte) interaction seems to play a critical role. Interestingly, DC express a functional CD40, which triggering upregulates expression of CD80 and CD86 and induces cytokine production, indicating a reciprocal talk between DC and T cells during the course of antigen presentation. Finally, in vitro generated DC interact directly with B cells, activated through their CD40 antigen, leading to enhanced growth, differentiation (IgM production) and preferential isotype switch towards IgA. Thus, in the extrafollicular area of secondary lymphoid organs, in addition to prime naive T cells, DC might also directly provide costimulatory signals involved during the initiation of primary B cell responses.

Animals↗

PubMed1997

Dendritic cells enhance growth and differentiation of CD40-activated B lymphocytes.

After antigen capture, dendritic cells (DC) migrate into T cell-rich areas of secondary lymphoid organs, where they induce T cell activation, that subsequently drives B cell activation. Here, we investigate whether DC, generated in vitro, can directly modulate B cell responses, using CD40L-transfected L cells as surrogate activated T cells. DC, through the production of soluble mediators, stimulated by 3- to 6-fold the proliferation and subsequent recovery of B cells. Furthermore, after CD40 ligation, DC enhanced by 30-300-fold the secretion of IgG and IgA by sIgD- B cells (essentially memory B cells). In the presence of DC, naive sIgD+ B cells produced, in response to interleukin-2, large amounts of IgM. Thus, in addition to activating naive T cells in the extrafollicular areas of secondary lymphoid organs, DC may directly modulate B cell growth and differentiation.

Animals↗

PubMed1997

Apoptosis and the B cell response to antigen.

The primary B cell response to T cell dependent antigens comprises two pathways of differentiation; one resulting in formation of foci of antibody forming cells in the extrafollicular regions of secondary lymphoid organs and the other giving rise to germinal centers within the follicles. Foci of antibody forming cells are detectable for only a limited time, before involuting due to apoptosis of the plasma cells. Similarly in the germinal center, regulation of cell number, selection of high affinity variants generated by somatic hypermutation, and the resolution of the germinal center itself all involve the death of unwanted B cells. In this review we describe recent experiments which have allowed determination of the role of certain forms of apoptosis in the B cell response to antigen.

Animals↗

PubMed1997

Human interdigitating dendritic cells directly stimulate CD40-activated naive B cells.

Human interdigitating dendritic cells (IDC) were isolated from tonsils based on their CD40+ lineage-negative expression in situ. Isolated IDC displayed a phenotypic profile similar to that of IDC in tonsils and spleen in situ, characterized by high-level expression of major histocompatibility complex class II, the co-stimulatory molecules B7.1 (CD80) and B7.2 (CD86), expression of the late DC maturation marker CD83, and no expression of CD1a, CD13, or CD33. IDC also showed weak nonspecific esterase staining and had the ability to induce an allogeneic mixed lymphocyte reaction. In this study, we further show that in the presence of surrogate activated T cells in the form of CD40 ligation and IL-2, IDC enhance the proliferation of naive B cells and induce their differentiation into plasma cells producing IgM. Evidence for the anatomical co-localization of naive B cells and IDC in the T cell area together with the data obtained in vitro implies a role for IDC in the initiation of the extrafollicular reaction.

B-Lymphocytes↗

PubMed1998

An in vitro approach for the characterization of the cycling B cell response.

Because isolation of sufficient numbers of cycling, germinal center B cells from mice for biochemical characterization of BCR-derived signals can be problematic, we have designed an experimental approach for generating large numbers of cycling B cells for further study. In the experiments reported here, small, resting B cells were polyclonally stimulated with lipopolysaccharide (LPS), and cycling B cells isolated as two bands on three-step Percoll gradients. Cycling B cells isolated at Days 2, 4, or 6 of preactivation showed an increased expression of Fas receptor and peanut agglutinin binding, with a concomitant decrease in sIgD positivity. These cells phenotypically resembled extrafollicular or early germinal center B cells. These cycling B cells were used to study the functional consequences of differential signaling through the BCR. Strong cross-linking of BCR, by restimulation of cycling normal B cells with either immobilized or soluble F(ab')2 anti-mu and cycling hen egg lysozyme (HEL) transgenic B cells with either soluble or immobilized HEL, extended cellular proliferation by 2-3 d. In contrast, cycling B cells either restimulated with soluble, whole anti-mu (to mimic binding of soluble immune complexes) or cultured in the absence of restimulation (to mimic cycling B cells not competitive for antigen) resulted in the rapid exit of the cells from cycle. This system will enable the molecular and biochemical characterization of signal delivery to cycling B cells.

Animals↗

PubMed1992

[Expression of beta 1 integrins in normal B lymphocytes at different stages of development and in B cell neoplasias].

VLA-1 to -6 are cell surface molecules binding to matrix molecules such as collagen, fibronectin, epiligrin, and laminin. In addition, VLA-4 binds to VCAM-1 and ICAM-2, thus mediating intercellular adhesion prerogative for lymphocyte extravasation or "homing". Using frozen tissue of normal lymphoid organs and of 100 morphologically and immunologically typed B cell neoplasias, monoclonal antibodies to all six VLA-alpha subunits and to the common beta 1-chain were applied to serial sections. VLAs were found differentially expressed in cytologically and microtopographically defined B cell subsets [follicular mantle zone cells (MZ), follicular center cells (FC), extrafollicular cells (EF), and plasma cells (PC)] of normal spleen, lymph node, and thymic medulla (which contains an EF compartment). Thus, these cell types, which correspond to discrete stages of B cell development, can also be defined by their VLA status. Acute B lymphoblastic leukemia (ALL) was VLA-1-, 2-, 3 +/-, 4 +/-, 5 +/-, 6-. The VLA-1-, -2 +/-, -3+, -4+, -5+, -6- phenotype of chronic B lymphocytic leukemia (CLL) resembled that of MZ. Hairy cell leukemia (HCL) differed from CLL in its tendency to lack VLA-2, in its consistent lack of VLA-3, and altogether resembled splenic EF in its VLA profile. Mantle zone lymphoma (MZL) consistently expressed VLA-3 and -4 and frequently VLA-5. Nodal follicular center cell lymphomas (FCCL) were VLA-1- and -2- and very rarely expressed VLA-5 and -6. Thus, FCCL although roughly corresponding to FC, tended to aberrantly express VLA-3 and/or VLA-4. Burkitt's lymphoma resembled FCCL but expressed VLA-4 more frequently and at higher levels.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗

PubMed1992

Adhesion molecules VLA-1 to VLA-6 define discrete stages of peripheral B lymphocyte development and characterize different types of B cell neoplasia.

VLA-1 to VLA-6 are cell-surface molecules binding to matrix molecules such as collagen, fibronectin, epiligrin, and laminin. In addition, VLA-4 binds to VCAM-1 and ICAM-2, thus mediating intercellular adhesion prerogative for lymphocyte extravasation or 'homing'. Using frozen tissue of normal lymphoid organs and of 100 morphologically and immunologically typed B cell neoplasias, monoclonal antibodies to all six VAL-alpha and to the common beta-chain were applied to serial sections. VLAs were found differentially expressed in cytologically and microtopographically defined B-cell subsets [follicular mantle zone cells (MZ), follicular center cells (FC), extrafollicular cells (EF), and plasma cells (PC)] of normal spleen, lymph node, and thymic medulla (which contains an EF compartment). Thus, these cell types, which correspond to discrete stages of B cell development, can also be defined by their VLA status. Acute B lymphoblastic leukemia (ALL) was VLA-1-, 2-, 3 +/-, 4 +/-, 5 +/-, 6-. The VLA-1-, -2 +/-, 3+, -4+, -5+, -6-phenotype of chronic B lymphocytic leukemia (CLL) resembled that of MZ. Hairy cell leukemia (HCL) differed from CLL in its tendency to lack VLA-2, in its consistent lack of VLA-3, and altogether resembled splenic EF in its VLA profile. Mantle zone lymphoma (MZL) consistently expressed VLA-3 and -4 and frequently VLA-5. Nodal follicular center cell lymphomas (FCCL) were VLA-1- and -2- and very rarely expressed VLA-5 and -6. Thus, FCCL although roughly corresponding to FC, tended to aberrantly express VLA-3 and/or VLA-4. Burkitt's lymphoma resembled FCCL but expressed VLA-4 more frequently and at higher levels. Mediastinal clear cell lymphoma of B-cell type differed from FCCL in its regular lack of VLA-3, -5, and -6 and in frequently lacking VLA-4. Medullary plasmacytoma was VLA-1-, -2-, -3 +/-, -4 +/-, -5-, -6+, thus being the only B cell neoplasia which was consistently VLA-6+. With respect to the well-known clinical characteristics of the B cell malignancies examined, the leukemic phenotype might crucially depend on the presence of VLA-5.

B-Lymphocytes↗

PubMed1991

Phenotype and topography of human thymic B cells. An immunohistologic study.

Using single and double labeling immunohistochemical techniques and a large panel of monoclonal antibodies against B-cell differentiation antigens, including those newly defined at the Fourth International Leucocyte Typing Workshop, we have examined the immunophenotype and tissue distribution of human thymic B-cells. The existence of a distinct B-cell population as a constant constituent of the thymic microenvironment has been noted only recently. We found a significant population of B-lymphocytes in the thymic medulla expressing the B-cell restricted antigens CD19, CD20, CD22, CD37, CD72, CD76 and IgM and IgD. As with other extrafollicular B-lymphocytes, they differ significantly from both follicle mantle and germinal center cells in morphology and immunophenotype, which points to alternative modes of B-cell differentiation. Thymic B-cells themselves show considerable heterogeneity and a subpopulation with dendritic features and the expression of CD23 has been referred to as "asteroid" cells. Their close association with T-cells and medullary epithelial cells points to a functional role for B-cells in the thymus. A second population of B-lymphocytes together with frequent lymph follicles is found within the extrathymic perviascular space. Though separated from the medulla by a layer of epithelial cells, a clear distinction between the B-cells of these two compartments is not always possible. The intramedullary B-cell compartment shows a parallel numeric increase with the occurrence of germinal centers in the perivascular space, mostly due to an accumulation of B-cells in the medulla adjacent to these lymph follicles. Thus a close relationship between the intra- and extramedullary B-cell population of the thymus seems likely.

Adolescent↗