Protection of T cells from activation-induced cell death by Fas+ B cells

Abstract

Naive CD4+ T cells proliferate strongly in response to stimulation by superantigens such as staphylococcal enterotoxin B (SEB). However, when these same cells revert to a resting phenotype and are subjected to restimulation with either SEB or anti-CD3, the majority of these SEB-responsive cells undergo Fas ligand (FasL)-mediated activation-induced cell death (AICD). We investigated the impact of Fas expression on T cell AICD by utilizing B cell stimulators that lacked functional FasL and either expressed or did not express the Fas receptor. Our results indicate that B cells play an important role in modulating the level of T cell AICD via the Fas/FasL pathway. Activated B cells expressing high levels of Fas receptor can redirect the FasL expressed by T cells primed to undergo AICD away from the T cells and prevent the induction of AICD in these cells. Furthermore, B cells stimulated through both the CD40 receptor and membrane IgM appear to mediate a stronger protective effect on T cells by virtue of their resistance to FasL-mediated cytolysis. These observations suggest a mechanism by which normal B cell and T cell responses to foreign antigen are maintained, while responses to self antigen are not.

Receptor‐specific regulation of B‐cell susceptibility to Fas‐mediated apoptosis and a novel Fas apoptosis inhibitory molecule

“…Along the same lines it might be predicted that Fas-resistant B cells would competitively inhibit activationinduced cell death (AICD), in which T cells constitute the targets for Th1 CMC. Indeed, this was recently demonstrated in vitro (59), suggesting that inducible Fas resistance in B cells may help perpetuate T, as well as B, cell responses. The concept that Fas resistance modulates B and T-cell deletion and B and T-cell responses is further supported, albeit indirectly, by the durability of the receptor-specific phenotype, as it was found that susceptibility to Fas-mediated apoptosis of B cells treated with CD40L plus anti-Ig (Fas-resistant), or treated with CD40L alone (Fas-sensitive), did not change when B cells were washed and recultured for 24 h in medium prior to assay of Th1 CMC.…”

The elusive identity of T follicular helper cells

“…Thus, migration into follicles might not be an exclusive property of Tfh cells, but might also be important for normal T cell expansion and generation of T cell memory. Furthermore, there is evidence to show that the follicle is the crucial niche for the optimal expansion and survival of activated T cells [35][36][37].…”