Circulating human CD27-IgA+ memory B cells recognize bacteria with polyreactive Igs

Magdalena A. Berkowska, Jean Nicolas Schickel, Christina Grosserichter-Wagener, Dick De Ridder, Yen Shing Ng, Jacques J.M. Van Dongen, Eric Meffre, Menno C. Van Zelm*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

47 Citations (Scopus)

Abstract

The vast majority of IgA production occurs in mucosal tissue following T cell-dependent and T cell-independent Ag responses. To study the nature of each of these responses, we analyzed the gene-expression and Ig-reactivity profiles of T cell-dependent CD27+ IgA+ and T cell-independent CD27-IgA+ circulating memory B cells. Gene-expression profiles of IgA+ subsets were highly similar to each other and to IgG+ memory B cell subsets, with typical upregulation of activation markers and downregulation of inhibitory receptors. However, we identified the mucosa-associated CCR9 and RUNX2 genes to be specifically upregulated in CD27-IgA+ B cells.We also found that CD27-IgA+ B cells expressed Abs with distinct Ig repertoire and reactivity compared with those from CD27+IgA+ B cells. Indeed, Abs from CD27-IgA+ B cells were weakly mutated, often used Igl chain, and were enriched in polyreactive clones recognizing various bacterial species. Hence, T cell-independent IgA responses are likely involved in the maintenance of gut homeostasis through the production of polyreactive mutated IgA Abs with cross-reactive anticommensal reactivity.

Original languageEnglish
Pages (from-to)1417-1426
JournalThe Journal of Immunology
Volume195
Issue number4
DOIs
Publication statusPublished - 2015

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