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Selective involvement of the Fas (CD95) / Fas ligand pathway in bone marrow B cell progenitors

Abstract : B lymphocyte generation in bone marrow (BM) compensates for cell loses. The Fas / Fas ligand (FasL) pathway has been implicated in apoptosis of various cell types. Abnormalities of the Fas receptor or of FasL expression are associated with excessive T cell proliferation and autoimmunity. To examine the role of the Fas / FasL system in B cell differentiation, we created double‐chimeric mice by transferring both C57BL / 6 (B6)‐Fas+ and lpr‐FasL+ BM cells into RAG‐2– / – hosts. Equal numbers of stem cells were co‐injected into sublethally irradiated recipients, and their progeny were studied by using antibodies directed against the B6‐Ly5.1+5.2+ and lpr‐Ly5.1–5.2+ populations. A longitudinal study lasting for up to 6 months revealed that cells of the lpr phenotype dominated the B6 phenotype in the BM, as a result of their active proliferation. Analysis of the B cell compartment showed more lpr than B6 cells among immature HSAhiB220lo populations. In contrast, the lpr and B6 phenotypes were equally represented among mature B cells. BM transfer to second hosts indicated that B6‐derived B cell progenitors were absent from the first host. These data suggest that activation of the Fas / FasL pathway disturbs the early steps of B cell development and might therefore contribute to the onset of autoimmune disorders.
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Submitted on : Monday, January 28, 2019 - 2:48:06 PM
Last modification on : Wednesday, October 14, 2020 - 3:58:35 AM

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Yasmina Laouar, Florence Vasseur, Géraldine Moreau, Corinne Garcia, Valerie Pasqualetto, et al.. Selective involvement of the Fas (CD95) / Fas ligand pathway in bone marrow B cell progenitors. European Journal of Immunology, Wiley-VCH Verlag, 2000, 30 (5), pp.1402-1409. ⟨10.1002/(SICI)1521-4141(200005)30:5<1402::AID-IMMU1402>3.0.CO;2-B⟩. ⟨hal-01996561⟩

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