Selective involvement of the Fas (CD95)/Fas ligand pathway in bone marrow B cell progenitors.
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 HSA(hi)B220(lo) 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.
Laouar
Y
Y
INSERM U345, Institut Necker, Paris, France.
Vasseur
F
F
Moreau
G
G
Garcia
C
C
Pasqualetto
V
V
Waché
A C
AC
Ezine
S
S
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology; D019014:fas Receptor / Q000276:immunology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor