Natural killer T cells and innate immune B cells from lupus‐prone NZB/W mice interact to generate IgM and IgG autoantibodies

Abstract

Lupus‐prone NZB/W F1 mice develop glomerulonephritis after T helper cell‐dependent isotype switching of autoantibody secretion from IgM to IgG at about 6 months of age. We compared innate immune natural killer (NK) T cells and conventional T cells for their capacity to help spontaneous in vitro immunoglobulin and autoantibody secretion of innate immune (B‐1 and marginal zone) and conventional (follicular) B cell subsets from NZB/W F1 mice. We found that purified NKT cells not only increased spontaneous secretion of IgM and IgM anti‐double‐stranded (ds)DNA antibodies by B‐1 and marginal zone B cells, but also facilitated secretion of IgG anti‐dsDNA antibodies predominantly by B‐1 B cells. Few IgM or IgG anti‐dsDNA antibodies were secreted by follicular B cells, and conventional T cells failed to provide potent helper activity to any B cell subset. All combinations of T and B cell subsets from normal C57BL/6 mice failed to generate vigorous IgM and IgG secretion. NZB/W NKT cell helper activity was blocked by anti‐CD1 and anti‐CD40L mAb. In conclusion, direct interactions between innate immune T and B cells form a pathway for the development of IgM and IgG lupus autoantibody secretion in NZB/W mice.