Mutual inhibition between Prkd2 and Bcl6 controls T follicular helper cell differentiation

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Science Immunology  24 Jan 2020:
Vol. 5, Issue 43, eaaz0085
DOI: 10.1126/sciimmunol.aaz0085

Kinase-regulated TFH differentiation

The Bcl6 transcription factor plays a key role in directing the differentiation of T follicular helper cells (TFH) that support B cell antibody production and germinal center (GC) formation. Misawa et al. used a genetic screen in mice to identify a mutation in protein kinase D2 (Prkd2), a serine/threonine kinase, which resulted in enhanced basal and post-immunization levels of serum IgE. Mice with the Prkd2 mutation and Prkd2-deficient mice developed hypergammaglobulinemia and anti-DNA antibodies due to a T cell–intrinsic defect causing TFH expansion and an increase in GCs. Phosphorylation of Bcl6 by Prkd2 inhibited Bcl6 nuclear translocation and TFH differentiation. These findings provide fresh insight into the complex regulatory pathways controlling TFH differentiation by naïve T cells activated through their T cell receptor.

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