IL-10 selectively regulates murine Ig isotype switching

A role for IL-10 in regulating Ig isotype switching directly at the level of the murine B cell has not been previously reported, In this report we show that IL-10 selectively up-regulated IgM to IgG3 class switching in lipopolysaccharide (LPS)-activated cultures through a direct effect on membrane (m) IgM(+)IgG3(-) B cells in vitro. IL-10 stimulated 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 transforming growth factor-beta-mediated generation of mIgA(+) cells and S-mu-S-alpha DNA rearrangement events in LPS-, but not CD40 ligand (CD40L)-activated B cells, This effect was not accompanied by changes in the steady-state levels of germline C-H alpha RNA. IL-10 had no effect 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 switching to particular murine Ig isotypes but it differs from most other murine cytokines in that its effects on switching do not appear to be associated with changes in the corresponding steady-state levels of germline C-H RNA.