B Lymphopoiesis in the Thymus

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
The Journal of Immunology (Impact Factor: 4.92). 06/2000; 164(10):5221-6. DOI: 10.4049/jimmunol.164.10.5221
Source: PubMed


The thymus has been regarded as the major site of T cell differentiation. We find that in addition to alphabeta and gammadelta T cells, a significant number (approximately 3 x 104 per day) of B220+IgM+ mature B cells are exported from the thymus of C57BL/6 mice. Of these emigrating B cells, we estimate that at least approximately 2 x 104 per day are cells which developed intrathymically, whereas a maximum of approximately 0.8 x 104 per day are cells which circulated through the thymus from the periphery. The thymus possesses a significant number of pro-B and pre-B cells that express CD19, VpreB, lambda5, and pax-5. These B cell progenitors were found in the thymic cortex, whereas increasingly mature B cells were found in the corticomedullar and medullary regions. Other lymphoid cells, including NK cells and lymphoid dendritic cells, are not exported from the thymus at detectable levels. Thus, the thymus contributes to the formation of peripheral pools of B cells as well as of alphabeta and gammadelta T cells.

Download full-text


Available from: William H. Carr, Jul 10, 2014
  • Source
    • "Based upon previous reports on intrathymic B lymphopoiesis (Akashi et al., 2000), we considered that Aire expression might be an intrinsically programmed feature of an intrathymically differentiating B lineage. Around one third of CD19 + thymic B cells were surface IgM – IgD – and thereby resembled B cell precursors in the BM (Figure 2A). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Thymic antigen-presenting cells (APCs) such as dendritic cells and medullary thymic epithelial cells (mTECs) use distinct strategies of self-antigen expression and presentation to mediate central tolerance. The thymus also harbors B cells; whether they also display unique tolerogenic features and how they genealogically relate to peripheral B cells is unclear. Here, we found that Aire is expressed in thymic but not peripheral B cells. Aire expression in thymic B cells coincided with major histocompatibility class II (MHCII) and CD80 upregulation and immunoglobulin class-switching. These features were recapitulated upon immigration of naive peripheral B cells into the thymus, whereby this intrathymic licensing required CD40 signaling in the context of cognate interactions with autoreactive CD4(+) thymocytes. Moreover, a licensing-dependent neo-antigen selectively upregulated in immigrating B cells mediated negative selection through direct presentation. Thus, autoreactivity within the nascent T cell repertoire fuels a feed forward loop that endows thymic B cells with tolerogenic features. Copyright © 2015 Elsevier Inc. All rights reserved.
    Immunity 06/2015; 42(6). DOI:10.1016/j.immuni.2015.05.013 · 21.56 Impact Factor
  • Source
    • "Subsequently, phycoerythrin staining demonstrated that approximately 3 × 104 cells/day emigrate from the adult mice thymus, showing a T cell-unrelated phenotype. These emigrant cells express IgM and B220 molecules and are therefore characterized as mature B cells [49]. In the same study, it was demonstrated that the majority of thymic B cells matured in the thymus, and only a minority of this population constituted infiltrated B cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A variety of mechanisms are involved in the regulation of offspring allergy development through maternal immunization with allergens. The passive transfer of antigens, antibodies, and cytokines, the induction of phenotypic alterations in offspring lymphocytes, and the induction of regulatory populations in offspring have been proposed, but these mechanisms remain incompletely understood. It is likely that maternal immunization could affect the intrathymic maturation of offspring TCD4+, TCD8+, γδT, nTreg, iNKT, and B lymphocytes, although there are currently no human maternal immunization protocols for the regulation of allergic responses in children. Some studies have suggested a direct interaction between the maternal immune status and the offspring intrathymic microenvironment; this interaction could influence the maturation of offspring regulatory cells and must be explored for the development of therapies to control allergy development in children.
    Research Journal of Immunology 06/2014; 2014(5):780386. DOI:10.1155/2014/780386
  • Source
    • "The absence of a phenotypically recognizable epithelial stroma indicate that a yet unidentified stromal cell type is permissive for thymocyte homing or developing in the human adenoidal tissue. Immature B-lymphopoiesis may require a more promiscuous or ubiquitous milieu, since they can be observed in the tonsils, adenoids, lymph nodes, spleen [10], [11], [13] and even thymus [29]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Adenoidal tissue (also known as nasopharyngeal tonsils) of 58% of humans in the pediatric age group contains immature T-lymphoid cells with the phenotype of thymocytes (TdT+,CD1abc+, cytoplasmic CD3+, coexpressing CD4 and CD8, lacking an Intraepithelial Lymphocyte-associated phenotype). The notable difference in comparison to palatine tonsils is the clustering in groups and sheets, comprising hundreds or thousands of cells (1.7%±0.2 of total T cells). The thymic epithelium is morphologically and phenotypically absent. Adenoids share with tonsils and lymph nodes the presence of immature B cell precursors (TdT+, CD1a-, Pax5+, Surrogate light chain±), however in these latter the presence of TdT+, CD1a+, Pax5- precursors is absent or limited to individual cells. Human adenoids are distinct among the Waldeyer's ring lymphoid tissue because of the known embryogenic derivation from the third pharyngeal pouch, from which the thymus develops; in addition, they may display phenotypic incomplete features of a vestigial thymus.
    PLoS ONE 05/2014; 9(5):e98222. DOI:10.1371/journal.pone.0098222 · 3.23 Impact Factor
Show more