TY - JOUR
T1 - Circulating human CD27-IgA+ memory B cells recognize bacteria with polyreactive Igs
AU - Berkowska, Magdalena A.
AU - Schickel, Jean Nicolas
AU - Grosserichter-Wagener, Christina
AU - De Ridder, Dick
AU - Ng, Yen Shing
AU - Van Dongen, Jacques J M
AU - Meffre, Eric
AU - Van Zelm, Menno C.
PY - 2015/8/15
Y1 - 2015/8/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84938922408&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1402708
DO - 10.4049/jimmunol.1402708
M3 - Article
C2 - 26150533
AN - SCOPUS:84938922408
SN - 0022-1767
VL - 195
SP - 1417
EP - 1426
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -