Expression and function of the murine CD95/FasR/APO-1 receptor in relation to B cell ontogeny.
Mice defective in Fas-mediated apoptosis (lpr phenotype) have an intrinsic B cell abnormality that predisposes them to autoantibody production. To investigate potential roles for the Fas receptor (FasR) in B cell tolerance, FasR expression and function were evaluated at different stages of B cell development. FasR expression was very low or absent on pro- and pre-B cells, but was detected in early B cell lines and was up-regulated following IFN-gamma-induced maturation of the pre-B cell line 70-Z. Whereas FasR expression was very low in resting mature sIgM+ B cells, expression was markedly increased following mitogen activation and was also elevated in two mature sIgG+ lymphoma lines. FasR expression correlated strongly with the ability of B cells to undergo Fas-mediated apoptosis. In addition, although Fas did not appear to play a direct role in apoptosis mediated by cross-linking of sIg with anti-IgM, anti-FasR and sublethal concentrations of anti-Ig were additive in the induction of apoptosis in the early B cell line WEHI 231. These findings suggest that the Fas pathway is not involved in the elimination of pro- and pre-B cells, but are compatible with an ancillary role for FasR in the elimination of early B cells and elimination of mature B cells following activation.
Onel
K B
KB
Specialized Center of Research (SCOR) in SLE, Hospital for Special Surgery-Cornell University Medical Center, New York, NY 10021, USA.
Tucek-Szabo
C L
CL
Ashany
D
D
Lacy
E
E
Nikolic-Zugic
J
J
Elkon
K B
KB
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D001854:Bone Marrow Cells; D002455:Cell Division; D019070:Cell Lineage; D007108:Immune Tolerance; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007152:Immunologic Capping; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008221:Lymphoid Tissue / Q000166:cytology; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D000888:Antibodies, Anti-Idiotypic; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C048844:anti-IgG; C044203:anti-IgM; D019014:fas Receptor