TY - JOUR
T1 - Natural anti-intestinal goblet cell autoantibody production from marginal zone B cells
AU - Ichikawa, Daiju
AU - Asano, Masanao
AU - Shinton, Susan A.
AU - Brill-Dashoff, Joni
AU - Formica, Anthony M.
AU - Velcich, Anna
AU - Hardy, Richard R.
AU - Hayakawa, Kyoko
N1 - Publisher Copyright:
Copyright © 2015 by The American Association of Immunologists, Inc.
PY - 2015/1/15
Y1 - 2015/1/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1402383
DO - 10.4049/jimmunol.1402383
M3 - Article
C2 - 25480561
AN - SCOPUS:84920454779
VL - 194
SP - 606
EP - 614
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -