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 intri nsic B cell abnormality that predisposes them to autoantibody producti on. To investigate potential roles for the Fas receptor (FasR) in B ce ll 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 wa s up-regulated following IFN-gamma-induced maturation of the pre-B cel l line 70-Z. Whereas FasR expression was very low in resting mature sI gM(+) B cells, expression was markedly increased following mitogen act ivation and was also elevated in two mature sIgG(+) lymphoma lines. Fa sR expression correlated strongly with the ability of B cells to under go 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 addi tive 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 eli mination 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.