Restraint of B cell activation by Foxj1-mediated antagonism of NF-kappa B and IL-6.

The forkhead transcription factor Foxj1 inhibits spontaneous autoimmunity, in part by antagonizing NF-kappaB activation in T cells. We demonstrate here that Foxj1 also inhibits humoral immune responses intrinsically in B cells; Foxj1 deficiency in B cells results in spontaneous and accentuated germinal center formation, associated with the development of pathogenic autoantibodies and accentuated responses to immunizations-all reflecting excessive activity of NF-kappaB and its target gene IL-6, and correlating with a requirement for Foxj1 to regulate the inhibitory NF-kappaB component IkappaBbeta. Thus, Foxj1 restrains B cell activation and the maturation of humoral responses, demonstrating a critical role for at least this forkhead transcription factor in the regulation of B lymphocyte homeostasis.