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Ichikawa D , Asano M , Shinton SA , Brill-Dashoff J , Formica AM , Velcich A , Hardy RR , Hayakawa K
Natural anti-intestinal goblet cell autoantibody production from marginal zone B cells
J Immunol. 2015 Jan 15;194(2) :606-14
PMID: 25480561    PMCID: PMC4282382   
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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 mukappa 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.
1550-6606 Ichikawa, Daiju Asano, Masanao Shinton, Susan A Brill-Dashoff, Joni Formica, Anthony M Velcich, Anna Hardy, Richard R Hayakawa, Kyoko R01 AI026782/AI/NIAID NIH HHS/United States R01 AI049335/AI/NIAID NIH HHS/United States R01 CA129330/CA/NCI NIH HHS/United States Journal Article United States J Immunol. 2015 Jan 15;194(2):606-14. doi: 10.4049/jimmunol.1402383. Epub 2014 Dec 5.