Activation of the Transcription Factor c-Maf in T Cells Is Dependent on the CARMA1-IKKβ Signaling Cascade

The proto-oncogene c-Maf is a transcription factor that plays a critical role in the differentiation of various T helper (T-H) cell subsets. The amount of c-Maf increases after stimulation of the T cell receptor (TCR), which results in the production of multiple cytokines. We showed that two essential regulators of the transcription factor nuclear factor kappa B (NF-kappa B), the scaffold protein CARMA1 and the kinase IKK beta [inhibitor of NF-kappa B (I kappa B) kinase beta], are also critical for the activation of c-Maf. Although CARMA1 deficiency did not affect the TCR-dependent increase in c-Maf abundance in T cells, CARMA1-dependent activation of the IKK complex was required for the nuclear translocation of c-Maf and its binding to the promoters of its target genes. Consistent with a role for c-Maf in the development of T follicular helper (T-FH) cells, which provide help to B cells in the germinal centers of the spleen, CARMA1- or IKK beta-deficient mice immunized with peptide antigen had defects in the generation of T-FH cells, formation of germinal centers, and production of antigen-specific antibodies. Together, these data suggest a mechanism by which c-Maf is regulated during T cell activation and differentiation.