Gut T cell–independent IgA responses to commensal bacteria require engagement of the TACI receptor on B cells
Emilie K. Grasset, Alejo Chorny, Sandra Casas-Recasens, Cindy Gutzeit, Gerold Bongers, Irene Thomsen, Lili Chen, Zhengxiang He, Dean B. Matthews, Michael A. Oropallo, Pavan K. Veeramreddy, Mathieu Uzzan, Arthur Mortha, Jorge Carrillo, Bernardo Sgarbi Reis, Meera Ramanujam, Jordi Sintes, Giuliana Magri, Paul J. Maglione, Charlotte Cunningham‐Rundles, Richard J. Bram, Jeremiah J. Faith, Saurabh Mehandru, Oliver Pabst, Andrea Cerutti
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.