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Biology subjects

Haniuda, K.

Publications and source records attributed to Haniuda, K..

2 recordsLinked to original sources

Unconventionally primed type 1 follicular helper T cells are required for long-lived IgA plasma cell development following mucosal viral infection

Although IgA+ long-lived plasma cells (LLPCs) generated following mucosal viral infection provide durable protection against reinfection, little is known about their generation. Here, we show that oral RV infection induces gut-resident LLPCs that produce highly mutated protective IgA. Unlike RV-specific IgG+ LLPCs, IgA+ LLPCs were generated independently of MHCII expression by dendritic cells - rather MHCII expression by B cells was both necessary and sufficient. B cell MHCII was also sufficient to induce a unique population of T-bet+ follicular helper T (TFH1) cells which were crucial for RV-specific IgA+ LLPC accumulation in the gut via IFN{gamma}- and CXCR3-dependent mechanisms. Similar to RV infection, TFH1 cells were required for influenza-specific IgA response. However, unlike RV infection, B cell MHCII was not sufficient to induce influenza-specific IgA+ LLPCs, suggesting the operation of mucosal site-specific priming mechanisms. Collectively, our data reveal that unconventionally primed TFH1 cells support IgA responses to mucosal viral infections.

immunology↗

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

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.

immunology↗