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 differentiation. In mature B cells, CD40 mediates stimulation and costimulation of cell growth, switch recombination, and transcriptional regulation. CD40-mediated signaling also regulates cell death, rescuing B cells 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 as direct transcriptional regulators. Modulation of protein tyrosine kinase 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 differentiation stage-specific B cell responses.
Kehry
M R
MR
Department of Immunological Diseases, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefeild, CT 06877, USA.
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019013:CD40 Antigens / Q000378:metabolism*; D002455:Cell Division; D002470:Cell Survival; D006801:Humans; D008954:Models, Biological; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D048008:TNF Receptor-Associated Factor 3
D019013:CD40 Antigens; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D048008:TNF Receptor-Associated Factor 3; D011505:Protein-Tyrosine Kinases