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

First Author  Takahashi T Year  2008
Journal  Eur J Immunol Volume  38
Issue  1 Pages  156-65
PubMed ID  18050273 Mgi Jnum  J:130371
Mgi Id  MGI:3771529 Doi  10.1002/eji.200737656
Citation  Takahashi T, et al. (2008) Natural killer T cells and innate immune B cells from lupus-prone NZB/W mice interact to generate IgM and IgG autoantibodies. Eur J Immunol 38(1):156-65
abstractText  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.
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