Cross-Reactive Antigen Expressed by B6 Splenocytes Drives Receptor Editing and Marginal Zone Differentiation of IgG2a-Reactive AM14 Vκ8 B Cells.

Autor:	Nündel K; Department of Medicine, University of Massachusetts School of Medicine, Worcester, MA 01605., Mande P; Department of Medicine, University of Massachusetts School of Medicine, Worcester, MA 01605., Moses SL; Department of Medicine, University of Massachusetts School of Medicine, Worcester, MA 01605., Busto P; Department of Medicine, University of Massachusetts School of Medicine, Worcester, MA 01605., Cullen JL; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510., Schmidt MR; Department of Microbiology and Physiological Systems, University of Massachusetts School of Medicine, Worcester, MA 01605; and., Shlomchik MJ; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261., Woodland RT; Department of Microbiology and Physiological Systems, University of Massachusetts School of Medicine, Worcester, MA 01605; and., Marshak-Rothstein A; Department of Medicine, University of Massachusetts School of Medicine, Worcester, MA 01605.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2019 Oct 15; Vol. 203 (8), pp. 2055-2062.
DOI:	10.4049/jimmunol.1900499
Abstrakt:	The AM14 BCR, derived from an autoimmune MRL/lpr mouse, binds autologous IgG2aa/j with low affinity, and as a result, AM14 B cells only proliferate in response to IgG2a immune complexes that incorporate DNA, RNA, or nucleic acid-binding proteins that serve as autoadjuvants. As such, AM14 B cells have served as a useful model for demonstrating the importance of BCR/TLR coengagement in the activation of autoreactive B cells. We now show that the same receptor recognizes an additional murine-encoded Ag, expressed by B6 splenocytes, with sufficient avidity to induce a TLR-independent proliferative response of BALB/c AM14 Vκ8 B cells both in vivo and in vitro. Moreover, detection of this cross-reactive Ag by B6 AM14 Vκ8 B cells promotes an anergic phenotype as reflected by suboptimal responses to BCR cross-linking and the absence of mature B cells in the bone marrow. The B6 Ag further impacts B cell development as shown by a dramatically expanded marginal zone compartment and extensive receptor editing in B6 AM14 Vκ8 mice but not BALB/c AM14 Vκ8 mice. Despite their anergic phenotypes, B6 AM14 Vκ8 B cells can respond robustly to autoantigen/autoadjuvant immune complexes and could therefore participate in both autoimmune responses and host defense. (Copyright © 2019 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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