IL-10 SELECTIVELY REGULATES MURINE IG ISOTYPE SWITCHING

A role for IL-10 in regulating Ig isotype switching directly at the le vel of the murine B cell has not been previously reported, In this rep ort we show that IL-10 selectively up-regulated IgM to IgG3 class swit ching in lipopolysaccharide (LPS)-activated cultures through a direct effect on membrane (m) IgM(+)IgG3(-) B cells in vitro. IL-10 stimulate d a 3- to 4-fold enhancement (from 6-8 to 20-30%) in membrane mIgG3(+) cells and a significant increase in S-mu-S(gamma)3 DNA rearrangement events as measured by digestion-circularization PCR (DC-PCR) over that observed with LPS alone, IL-10 induction of switching to lgG3 was not accompanied by a corresponding increase in the steady-state levels of germline C(H gamma)3 RNA, By contrast, IL-10 strongly inhibited the t ransforming growth factor-beta-mediated generation of mIgA(+) cells an d S-mu-S-alpha DNA rearrangement events in LPS-, but not CD40 ligand ( CD40L)-activated B cells, This effect was not accompanied by changes i n the steady-state levels of germline C-H alpha RNA. IL-10 had no effe ct on IL-4-mediated switching to either IgG1 or IgE in either LPS- or CD40L-activated B cells, Thus, IL-10 can either enhance or suppress sw itching to particular murine Ig isotypes but it differs from most othe r murine cytokines in that its effects on switching do not appear to b e associated with changes in the corresponding steady-state levels of germline C-H RNA.