Sci. Signal., 17 December 2013
Determining T Cell FateT cell receptor (TCR)–dependent activation of the transcription factor nuclear factor B (NF-B) requires a complex containing the adaptor protein CARMA1, which results in the downstream activation of the inhibitor of NF-B (IB) kinase (IKK) complex, including IKKβ. Blonska et al. showed that CARMA1 and IKKβ perform double duty in also mediating the TCR-dependent activation of c-Maf, a transcription factor required for the development of T follicular helper (TFH) cells, which help B cells to make antibodies against various antigens. CARMA1 and IKKβ did not affect the abundance of c-Maf in TCR-activated T cells but were required for its phosphorylation and translocation to the nucleus in an NF-B–independent manner. Immunized mice deficient in either CARMA1 or IKKβ generated decreased numbers of TFH cells compared to immunized wild-type mice and had defective antibody production by B cells. Together, these data suggest that CARMA1 and IKKβ act outside the NF-B signaling axis to help determine T cell fate.
Citation: M. Blonska, D. Joo, R. I. Nurieva, X. Zhao, P. Chiao, S.-C. Sun, C. Dong, X. Lin, Activation of the Transcription Factor c-Maf in T Cells Is Dependent on the CARMA1-IKKβ Signaling Cascade. Sci. Signal. 6, ra110 (2013).
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