title: Autocrine IL-10 promotes human B-cell differentiation into IgM- or IgG-secreting plasmablasts.
abstract: B-cell-derived interleukin-10 (IL-10) is known to act in a paracrine fashion to suppress inflammation. Here, we show that IL-10 also acts in an autocrine manner to regulate the differentiation of activated human B cells. We report that IL-10 expression is not restricted to a dedicated B-cell subset, but is induced transiently in peripheral human naïve, memory, and CD5(+) B cells alike upon activation. Global transcriptome comparison of activated human B cells, secreting IL-10 or not, identified 138 differentially regulated genes, most of which were associated with differentiation into antibody-secreting cells and reflecting autocrine IL-10 signaling. We monitored the differentiation of IL-10-secreting B cells and determined the effect of IL-10-blocking antibodies against its autocrine and paracrine signaling. IL-10 signaling promoted the differentiation of activated IL-10-secreting B cells into IgM- or IgG-secreting cells, but was dispensable for IgA secretion. Our data imply that B-cell-derived IL-10 not only suppresses immune reactions via paracrine mechanisms, but can also contribute to the differentiation of IL-10-secreting B cells into IgM- and IgG-secreting plasmablasts through both autocrine and paracrine signaling.
authors.affiliation: Allergie-Centrum-Charité, CCM, Klinik für Dermatologie, Venerologie und Allergologie, Charité-Universitäts-medizin Berlin, Berlin, Germany; Cell Biology Group, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Berlin, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Heine
authors.forename: Gennadiy
authors.initials: G
authors.lastname: Drozdenko
authors.forename: Joachim R
authors.initials: JR
authors.lastname: Grün
authors.forename: Hyun-Dong
authors.initials: HD
authors.lastname: Chang
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Margitta
authors.initials: M
authors.lastname: Worm
mesh_terms: D019898:Autocrine Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology* / Q000378:metabolism; D007156:Immunologic Memory / Q000502:physiology; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D008297:Male; D019899:Paracrine Communication / Q000276:immunology*; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C508609:IL10 protein, human; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016753:Interleukin-10
keywords: Antibody-secreting cell; Human B cells; IL-10; Transcriptome