Gut T cell-independent IgA responses to commensal bacteria require engagement of the TACI receptor on B cells

肠道 T 细胞独立的 IgA 对共生菌的反应需要 B 细胞上的 TACI 受体的参与

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作者:E K Grasset, A Chorny, S Casas-Recasens, C Gutzeit, G Bongers, I Thomsen, L Chen, Z He, D B Matthews, M A Oropallo, P Veeramreddy, M Uzzan, A Mortha, J Carrillo, B S Reis, M Ramanujam, J Sintes, G Magri, P J Maglione, C Cunningham-Rundles, R J Bram, J Faith, S Mehandru, O Pabst, A Cerutti1

Abstract

The gut mounts secretory immunoglobulin A (SIgA) responses to commensal bacteria through nonredundant T cell-dependent (TD) and T cell-independent (TI) pathways that promote the establishment of mutualistic host-microbiota interactions. SIgAs from the TD pathway target penetrant bacteria, and their induction requires engagement of CD40 on B cells by CD40 ligand on T follicular helper cells. In contrast, SIgAs from the TI pathway bind a larger spectrum of bacteria, but the mechanism underpinning their production remains elusive. Here, we show that the intestinal TI pathway required CD40-independent B cell-activating signals from TACI, a receptor for the innate CD40 ligand-like factors BAFF and APRIL. TACI-induced SIgA responses targeted a fraction of the gut microbiota without shaping its overall composition. Of note, TACI was dispensable for TD induction of IgA in gut-associated lymphoid organs. Thus, BAFF/APRIL signals acting on TACI orchestrate commensal bacteria-specific SIgA responses through an intestinal TI program.

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