Fas apoptosis inhibitory molecule enhances CD40 signaling in B cells and augments the plasma cell compartment.
Fas apoptosis inhibitory molecule (FAIM) was cloned as a mediator of Fas resistance that is highly evolutionarily conserved but contains no known effector motifs. In this study, we report entirely new functions of FAIM that regulate B cell signaling and differentiation. FAIM acts to specifically enhance CD40 signaling for NF-kappaB activation, IRF-4 expression, and BCL-6 down-regulation in vitro, but has no effect on its own or in conjunction with LPS or anti-Ig stimulation. In keeping with its effects on IRF-4 and BCL-6, FAIM overexpression augments the plasma cell compartment in vivo. These results indicate that FAIM is a new player on the field of B cell differentiation and acts as a force multiplier for a series of events that begins with CD40 engagement and ends with plasma cell differentiation.
Kaku
Hiroaki
H
Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
Rothstein
Thomas L
TL
D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D001402:B-Lymphocytes; D019013:CD40 Antigens / Q000378:metabolism*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D015398:Signal Transduction; D000099218:Interferon Regulatory Factor-4
D051017:Apoptosis Regulatory Proteins; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D016328:NF-kappa B; D051560:Proto-Oncogene Proteins c-bcl-6; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human; C421307:FAIM protein, human