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

Daiju Ichikawa, Masanao Asano, Susan A. Shinton, Joni Brill-Dashoff, Anthony M. Formica, Anna Velcich, Richard R. Hardy, Kyoko Hayakawa

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 Vκ21-5/Jκ2 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 Vκ19-17/Jκ1 L chain rearrangement. This VH3609/Vκ19-17 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 μ κ 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 Tg B 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.

Original languageEnglish
Pages (from-to)606-614
Number of pages9
JournalJournal of Immunology
Volume194
Issue number2
DOIs
Publication statusPublished - 2015 Jan 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Ichikawa, D., Asano, M., Shinton, S. A., Brill-Dashoff, J., Formica, A. M., Velcich, A., Hardy, R. R., & Hayakawa, K. (2015). Natural anti-intestinal goblet cell autoantibody production from marginal zone B cells. Journal of Immunology, 194(2), 606-614. https://doi.org/10.4049/jimmunol.1402383