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Natural anti-intestinal goblet cell autoantibody production from marginal zone B cells.

Ichikawa D1, Asano M2, Shinton SA3, Brill-Dashoff J3, Formica AM3, Velcich A4, Hardy RR3, Hayakawa K5. J Immunol. 2015 Jan 15;194(2):606-14.

1Fox Chase Cancer Center, Philadelphia, PA 19111; Keio University Faculty of Pharmacy, Tokyo 105-8512, Japan;

2Fox Chase Cancer Center, Philadelphia, PA 19111; Juntendo University School of Medicine, Tokyo 113, Japan;

3Fox Chase Cancer Center, Philadelphia, PA 19111;

4Albert Einstein Cancer Center/Montefiore Medical Center, Bronx, NY 10467.and

5Fox Chase Cancer Center, Philadelphia, PA 19111; [email protected]

 

Abstract

Expression of a germline VH3609/D/JH2 IgH in mice results in the generation of B1 B cells with anti-thymocyte/Thy-1 glycoprotein autoreactivity by coexpression of Vk21-5/Jk2 L chain leading to production of serum IgM natural autoantibody. In these same mice, the marginal zone (MZ) B cell subset in spleen shows biased usage of a set of Ig L chains different from B1 B cells, with 30% having an identical Vk19-17/Jk1 L chain rearrangement. This VH3609/Vk19-17 IgM is reactive with intestinal goblet cell granules, binding to the intact large polymatrix form of mucin 2 glycoprotein secreted by goblet cells. Analysis of a μκ B cell AgR (BCR) transgenic (Tg) mouse with this anti-goblet cell/mucin2 autoreactive (AGcA) specificity demonstrates that immature B cells expressing the Tg BCR become MZ B cells in spleen by T cell-independent BCR signaling. These TgB cells produce AGcA as the predominant serum IgM, but without enteropathy. Without the transgene, AGcA autoreactivity is low but detectable in the serum of BALB/c and C.B17 mice, and this autoantibody is specifically produced by the MZ B cell subset. Thus, our findings reveal that AGcA is a natural autoantibody associated with MZ B cells.

Copyright © 2015 by The American Association of Immunologists, Inc.

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Natural anti-intestinal goblet cell autoantibody production from marginal zone B cells.. Global Medical Discovery