CD40 employs p38 MAP kinase in IgE isotype switching

IgE switching requires the prior induction of CE germline transcripts which is mediated by the concerted binding of STAT-6 and NF kappaB to the CE pro moter. These transcription factors are regulated by IL-4 and CD40, respecti vely. However the latter can effect other signaling pathways and the presen t study explores the role of p38 MAPK in induction of CE germline transcrip ts. CD40 and IL-4, both alone and in synergy, were initially shown to activ ate the CE promoter in a B cell lymphoma cell line. Under the same conditio ns CD40 caused activation of p38 MAPK, whereas IL-4 was ineffective. The p3 8 MAPK inhibitor, SB203580, and a dominant negative form of p38 MAPK decrea sed the CD40 activation of the CE promoter by reducing the ability of CD40 to increase the transactivation potential of NF kappaB. This study suggests that p38 MAPK is crucially important in mediating CD40 activation of NFKB which acts to induce CE germline transcripts, ultimately facilitating IgE s witching. (C) 2001 Academic Press.