B-CELL-DERIVED IL-10 - PRODUCTION AND FUNCTION

In vitro and in vivo studies identify IL-10 as a key cytokine that inh ibits cell-mediated immunity and inflammation while promoting humoral responses. The present review summarizes our studies regarding the abi lity of B cells to secrete IL-10. When established lines are considere d, 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 le vels of human IL-10, whereas viral IL-10 (encoded by EBV) remains unde tectable. Exogenous IL-10 enhances EBV-induced B-cell growth, while a neutralizing anti-IL-10 antibody inhibits it, suggesting that IL-10 ac ts as an autocrine growth factor for EBV-infected B lymphocytes. Norma l B lymphocytes secrete lower levels of human IL-10 following activati on through B-cell receptor or CD40 antigen. While addition of exogenou s IL-4 diminishes CD40-induced secretion of IL-10, addition of Staphyl occocus aureus Cowan I (SAC) particles increases it. Neutralization of endogenous IL-10 does not alter growth of CD40-activated 6 cells but inhibits their IgG, IgA, and IgM secretion, especially when costimulat ed with SAC particles. finally, the simultaneous blocking of both endo genous IL-10 and IL-6 Inhibits two-thirds of the production of the thr ee isotypes when B cells were triggered through CD40 in the presence o f 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 pathol ogies such as B-lymphoproliferative disorders and autoimmune diseases. (C) 1997 Academic Press, Inc.