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bioRxiv · 10.1101/2021.07.20.453051

Protein kinase Cδ is essential for the IgG response against T cell-independent type 2 antigens and commensal bacteria

Kitamura, D.·Fukao, S.·Haniuda, K.·Tamaki, H.
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Abstract

Antigens (Ags) with multivalent and repetitive structure elicit IgG production in a T cell-independent manner. However, the mechanisms by which such T cell-independent type-2 (TI-2) Ags induce IgG responses remain obscure. Here we report that BCR engagement with a TI-2 Ag but not with a T cell-dependent (TD) Ag was able to induce the transcription of activation-induced cytidine deaminase (AID) and efficient class switching to IgG3 upon co-stimulation with IL-1 or IFN-. TI-2 Ags strongly induced the phosphorylation of protein kinase C (PKC){delta} and PKC{delta} mediated the AID transcription through the induction of BATF, the key transcriptional regulator of AID expression. In PKC{delta}-deficient mice, production of IgG was intact against TD Ag but abrogated against typical TI-2 Ags as well as commensal bacteria, and experimental disruption of the gut epithelial barrier resulted in fatal bacteremia. Thus, our results revealed novel molecular requirements for class-switching in the TI-2 response and highlighted its importance in homeostatic commensal-specific IgG production.

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Kitamura, D., Fukao, S., Haniuda, K., Tamaki, H.. 2021-07-20. Protein kinase Cδ is essential for the IgG response against T cell-independent type 2 antigens and commensal bacteria. https://doi.org/10.1101/2021.07.20.453051

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