B-Cell-Derived IL-10: Production and Function

doi:10.1006/meth.1996.0393

Methods

Volume 11, Issue 1, January 1997, Pages 98-111

https://doi.org/10.1006/meth.1996.0393 Get rights and content

Abstract

In vitroandin vivostudies identify IL-10 as a key cytokine that inhibits cell-mediated immunity and inflammation while promoting humoral responses. The present review summarizes our studies regarding the ability of B cells to secrete IL-10. When established lines are considered, the production of human IL-10 is restricted to mature B-cell lines and correlates with Epstein–Barr Virus (EBV) expression. Accordingly, EBV infection induces purified tonsil B lymphocytes to produce high levels of human IL-10, whereas viral IL-10 (encoded by EBV) remains undetectable. Exogenous IL-10 enhances EBV-induced B-cell growth, while a neutralizing anti-IL-10 antibody inhibits it, suggesting that IL-10 acts as an autocrine growth factor for EBV-infected B lymphocytes. Normal B lymphocytes secrete lower levels of human IL-10 following activation through B-cell receptor or CD40 antigen. While addition of exogenous IL-4 diminishes CD40-induced secretion of IL-10, addition ofStaphyloccocus aureusCowan I (SAC) particles increases it. Neutralization of endogenous IL-10 does not alter growth of CD40-activated B cells but inhibits their IgG, IgA, and IgM secretion, especially when costimulated with SAC particles. Finally, the simultaneous blocking of both endogenous IL-10 and IL-6 inhibits two-thirds of the production of the three isotypes when B cells were triggered through CD40 in the presence of SAC particles, suggesting that IL-10 synergizes with IL-6 to sustain differentiation of CD40-activated B lymphocytes. Overexpression of B-cell-derived IL-10 is likely to contributein vivoto different pathologies such as B-lymphoproliferative disorders and autoimmune diseases.

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The expression analysis indicated that IL-10 might participate in host resistance to bacterial infection. In mammals, IL-10 promoted the proliferation and differentiation of activated B cells into plasma cells (Burdin et al., 1997). In addition, IL-10 also could regulate the differentiation of B cells and the secretion of total IgM antibodies in teleosts.
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IL-10 is one of the most important factors which promotes B cell proliferation and differentiation. It can promote the differentiation of B cells into antibody-secreting cells under the co-stimulation of IL-10 with other differentiation factors in mammals (Burdin et al., 1997; Moore et al., 2003) and teleost (He et al., 2012). In order to investigate the effects of OnCD38 expressions after IL-10 stimuli, leukocytes from head kidney were isolated and incubated with (r)OnIL-10 and (r)HomoIL-10, respectively.
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^☆: Ag, antigenBCR, B-cell receptor; APC, Antigen-presenting cell; CD40L, CD40 ligand; EBV, Epstein–Barr virus; ELISA, enzyme-linked-immunosorbent assay; IFN, interferon; Ig, immunoglobulins; sIg, surface Ig; IL-, interleukin-; Mb, monoclonal antibody; PCR, polymerase chain reaction; SAC, Staphyloccocus aureusCowan I;

¹: N. Burdin is the recipient of a grant from the Fondation Mérieux (Lyon, France).

²: To whom reprint requests should be addressed at Schering-Plough, Laboratory for Immunological Research, 27, Chemin des Peupliers, B.P. 11, 69571, Dardilly Cédex, France. Fax: (33) 478-35-47-50.

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Regular ArticleB-Cell-Derived IL-10: Production and Function☆

Abstract

Regular Article
B-Cell-Derived IL-10: Production and Function☆