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

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-RundlesR. J. Bram, J. Faith, S. Mehandru, O. Pabst, A. Cerutti, A. Cerutti

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number7117
JournalScience Immunology
Volume5
Issue number49
DOIs
StatePublished - Jul 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Grasset, E. K., Chorny, A., Casas-Recasens, S., Gutzeit, C., Bongers, G., Thomsen, I., Chen, L., He, Z., Matthews, D. B., Oropallo, M. A., Veeramreddy, P., Uzzan, M., Mortha, A., Carrillo, J., Reis, B. S., Ramanujam, M., Sintes, J., Magri, G., Maglione, P. J., ... Cerutti, A. (2020). Gut T cell-independent IgA responses to commensal bacteria require engagement of the TACI receptor on B cells. Science Immunology, 5(49), [7117]. https://doi.org/10.1126/SCIIMMUNOL.AAT7117