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Keywords:

  • FasR/APO-1;
  • Systemic lupus erythematosus;
  • Tolerance;
  • B lymphocytes

Abstract

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-γ-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.