Differential sensitivity to interleukins of CD5+ and CD5- anti-DNA antibody-producing B cells in murine lupus.

Abstract

We studied the effects of interleukins (IL) on in vitro IgM and IgG anti-DNA antibody production by splenic B cells from autoimmune disease-prone NZBxNZW (NZB/W) F1 mice. It was found that different interleukins regulate phenotypically distinct B cells producing separate isotype of anti-DNA antibodies. IL-2 slightly but significantly inhibited the production of IgM anti-DNA antibodies. IL-4 and IL-6 significantly enhanced the antibody production, but the effects were not so marked and inconsistent, particularly with respect to IL-6. By contrast, the effects of IL-5 were remarkable, particularly on splenic B cells from young mice. As for IgG anti-DNA antibodies, IL-6, but not other interleukins, markedly up-regulated the antibody production by splenic B cells from mice over 6 months of age, in a dose dependent fashion. Thus, the ability of B cells to produce IgG anti-DNA antibodies appears to be dependent on the surface expression of IL-6 receptor (IL-6R) at the ages when the mice begin to develop the disease. Studies of the surface phenotypes showed that while the IL-5-sensitive major IgM anti-DNA producers were CD5+Lp-3(CD43)-sIgM+, the IL-6-sensitive major IgG anti-DNA producers were CD5-Lp-3+sIgM-. However, significant amounts of IgG antibodies were also produced, in the presence of IL-6, by CD5+Lp-3+sIgM+, but not by CD5-Lp-3+sIgM+ B cells from 6-month-old mice. We suggest that surface phenotypes of anti-DNA antibody producers change from CD5+Lp-3-sIgM+IL-5R+, CD5+Lp-3+sIgM+IL-6R+ and subsequently to CD5-Lp-3+sIgM-(sIgG+)IL-6R+ in NZB/W F1 mice with aging.