title: Circulating Human CD27-IgA+ Memory B Cells Recognize Bacteria with Polyreactive Igs.
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 Igλ 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 anti-commensal reactivity.
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, 3015 CN Rotterdam, the Netherlands;
authors.forename: Magdalena A
authors.initials: MA
authors.lastname: Berkowska
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511; and.
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Schickel
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, 3015 CN Rotterdam, the Netherlands;
authors.forename: Christina
authors.initials: C
authors.lastname: Grosserichter-Wagener
authors.affiliation: The Delft Bioinformatics Lab, Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, 2628 CD Delft, the Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: de Ridder
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511; and.
authors.forename: Yen Shing
authors.initials: YS
authors.lastname: Ng
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, 3015 CN Rotterdam, the Netherlands;
authors.forename: Jacques J M
authors.initials: JJ
authors.lastname: van Dongen
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06511; and m.vanzelm@erasmusmc.nl eric.meffre@yale.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Meffre
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, 3015 CN Rotterdam, the Netherlands; m.vanzelm@erasmusmc.nl eric.meffre@yale.edu.
authors.forename: Menno C
authors.initials: MC
authors.lastname: van Zelm
mesh_terms: D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D001419:Bacteria / Q000276:immunology*; D016000:Cluster Analysis; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism; D054388:Receptors, CCR / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
chemical_list: C119309:CC chemokine receptor 9; D050659:Core Binding Factor Alpha 1 Subunit; D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007136:Immunoglobulins; D054388:Receptors, CCR; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7