Autocrine IL-10 promotes human B-cell differentiation into IgM- or IgG-secreting plasmablasts

Autor: Guido, Heine, Gennadiy, Drozdenko, Joachim R, Grün, Hyun-Dong, Chang, Andreas, Radbruch, Margitta, Worm
Rok vydání: 2013
Předmět:
Zdroj: European journal of immunology. 44(6)
ISSN: 1521-4141
Popis: 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.
Databáze: OpenAIRE