CD40-MEDIATED SIGNALING IN B-CELLS - BALANCING CELL-SURVIVAL, GROWTH,AND DEATH

Multimerization of CD40 molecules on B cells by binding CD40 ligand on activated T cells initiates signaling events essential for B cell dif ferentiation, In mature B cells, CD40 mediates stimulation and costimu lation of cell growth, switch recombination, and transcriptional regul ation, CD40-mediated signaling also regulates cell death, rescuing B c ells from anti-Ig-induced apoptosis and inducing the expression of the Fas surface molecule, Recent efforts to elucidate the biochemistry of CD40-mediated signaling pathways have identified members of the TRAF protein family that are associated with the cytoplasmic tail of CD40, CD40 cross-linking probably multimerizes TRAF proteins which may act a s direct transcriptional regulators, Modulation of protein tyrosine ki nase and protein tyrosine phosphatase activity also occurs after CD40- mediated signaling; however, a connection to the TRAF pathway has not been established, Multiple pathways of B cell triggering are probably integrated at the level of transcriptional activation to produce diffe rentiation stage-specific B cell responses.