The second way to anti-commensal IgA
Mammals rely on secretory IgA (SIgA) at the intestinal surface to maintain a homeostatic relationship with the commensal gut microbiota. B lymphocytes differentiate into IgA-producing plasma cells through a thymus-dependent pathway that depends on B cell CD40 transducing a signal from CD40 ligand on T cells. Grasset et al. investigated the contribution of the TACI receptor found predominantly on B cells to an alternative thymus-independent (TI) pathway of IgA+ plasma cell differentiation. Mice lacking both αβ and γδ T cell subsets had no germinal centers in their lymphoid tissues but still made SIgA antibodies that bound gut bacteria through a TI mechanism requiring TACI. These findings reveal that the mucosal immune system uses parallel pathways dependent on either CD40 or TACI to provide B cells the help needed to generate SIgA capable of binding commensal bacteria.
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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