B-cell-derived IL-10: production and function.
In vitro and in vivo studies 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 lym phocytes 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 of Staphyloccocus aureus Cowan 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 simul taneous 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 contribute in vivo to different pathologies such as B-lymphoproliferative disorders and autoimmune diseases.
Burdin
N
N
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Rousset
F
F
Banchereau
J
J
D000906:Antibodies / Q000494:pharmacology; D001402:B-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014170:Transformation, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D000906:Antibodies; D019013:CD40 Antigens; D007136:Immunoglobulins; D015850:Interleukin-6; D012333:RNA, Messenger; D016753:Interleukin-10