Y. Laouar et al., Selective involvement of the Fas (CD95)/Fas ligand pathway in bone marrow B cell progenitors, EUR J IMMUN, 30(5), 2000, pp. 1402-1409
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 Fast expression are ass
ociated with excessive T cell proliferation and autoimmunity. To examine th
e role of the Fas/FasL system in B cell differentiation, we created double-
chimeric mice by transferring both C57BL/6 (BG)-Fas(+) and Ipr-FasL(+) BM c
ells into RAG-2(-/-) hosts. Equal numbers of stem cells were cc-injected in
to sublethally irradiated recipients, and their progeny were studied by usi
ng antibodies directed against the B6-Ly5.1(+)5.2(+) and Ipr-Ly5.1(-)5.2(+)
populations. A longitudinal study lasting for up to 6 months revealed that
cells of the Ipr phenotype dominated the B6 phenotype in the BM, as a resu
lt of their active proliferation. Analysis of the B cell compartment showed
more Ipr than B6 cells among immature HSA(hi)B220(lo) populations. In cont
rast, the Ipr and B6 phenotypes were equally represented among mature B cel
ls. BM transfer to second hosts indicated that B6-derived B cell progenitor
s were absent from the first host. These data suggest that activation of th
e Fas/FasL pathway disturbs the early steps of B cell development and might
therefore contribute to the onset of autoimmune disorders.