|Title||Circulating human CD27-IgA+ memory B cells recognize bacteria with polyreactive Igs|
|Author(s)||Berkowska, Magdalena A.; Schickel, Jean Nicolas; Grosserichter-Wagener, Christina; Ridder, Dick De; Ng, Yen Shing; Dongen, Jacques J.M. Van; Meffre, Eric; Zelm, Menno C. Van|
|Source||The Journal of Immunology 195 (2015)4. - ISSN 0022-1767 - p. 1417 - 1426.|
|Publication type||Refereed Article in a scientific journal|
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.