Research ArticleImmunology

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

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Science Signaling  17 Dec 2013:
Vol. 6, Issue 306, pp. ra110
DOI: 10.1126/scisignal.2004273

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Determining T Cell Fate

T cell receptor (TCR)–dependent activation of the transcription factor nuclear factor κB (NF-κB) requires a complex containing the adaptor protein CARMA1, which results in the downstream activation of the inhibitor of NF-κB (IκB) 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-κB–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-κB signaling axis to help determine T cell fate.

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