Type I interferon promotes the fate of Toll-like receptor 9-stimulated follicular B cells to plasma cell differentiation

Higuchi, R; Tanaka, K; Saito, Y; Murakami, D; NAKAGAWA, T; Nutt, SL; Ohkawa, Y; Baba, Y

Author(s): Higuchi, R; Tanaka, K; Saito, Y; Murakami, D; NAKAGAWA, T; Nutt, SL; Ohkawa, Y; Baba, Y;
Details: Publication Year 2024-04,Volume 3,Issue #4,Page pgae152
Journal Title: PNAS Nexus
Abstract: The activation and differentiation of B cells into plasma cells (PCs) play critical roles in the immune response to infections and autoimmune diseases. Toll-like receptor 9 (TLR9) responds to bacterial and viral DNA containing unmethylated CpG motifs and triggers immune responses in B cells; however, abnormal recognition of self-DNA by TLR9 can cause autoimmune diseases. When stimulated with TLR9 agonists, follicular (FO) B cells, a subset of B cells residing in the FO regions of secondary lymphoid organs, exhibit a propensity for activation but fail to give rise to PCs. The factors that enable the transition of TLR9-activated FO B cells from activation to differentiation into PCs remain unclear. In this study, we show that type I interferon-alpha (IFNα) signaling causes FO B cells activated by CpG stimulation to differentiate into PCs. Although CpG stimulation alone only temporarily increased interferon regulatory factor 4 (IRF4) expression in FO B cells, co-stimulation with both CpG and IFNα enhanced and maintained high IRF4 expression levels, ultimately enabling the cells to differentiate into PCs. Overexpression of IRF4 in FO B cells results in CpG-induced PC transition without IFN signaling. Furthermore, co-stimulation of TLR9 and IFNα receptors significantly enhanced mammalian target of rapamycin (mTOR) signaling, which regulates IRF4 expression and PC generation. These findings suggest that IFNα may play a key role in promoting the fate of PC differentiation in FO B cells activated by TLR9 stimulation.
Publisher: Oxford Academic
Keywords: B cells; Irf4; Tlr9; plasma cells; type 1 IFN
Research Division(s): Immunology
PubMed ID: 38659975
Publisher's Version: https://doi.org/10.1093/pnasnexus/pgae152
Open Access at Publisher's Site: https://doi.org/10.1093/pnasnexus/pgae152
Terms of Use/Rights Notice: Refer to copyright notice on published article.
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Creation Date: 2024-05-08 10:06:36

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