Expression and function of the murine CD95/FasR/APO-1 receptor in relation to B cell ontogeny

✍ Scribed by Karen B. Onel; Carolyn L. Tucek-Szabo; Dalit Ashany; Elizabeth Lacy; Janko Nikolic-Zugic; Keith B. Elkon

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 897 KB
• Volume: 25
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830251034

✦ Synopsis

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.