title: Natural anti-intestinal goblet cell autoantibody production from marginal zone B cells.
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 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.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111; Keio University Faculty of Pharmacy, Tokyo 105-8512, Japan;
authors.forename: Daiju
authors.initials: D
authors.lastname: Ichikawa
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111; Juntendo University School of Medicine, Tokyo 113, Japan; and.
authors.forename: Masanao
authors.initials: M
authors.lastname: Asano
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111;
authors.forename: Susan A
authors.initials: SA
authors.lastname: Shinton
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111;
authors.forename: Joni
authors.initials: J
authors.lastname: Brill-Dashoff
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111;
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Formica
authors.affiliation: Albert Einstein Cancer Center/Montefiore Medical Center, Bronx, NY 10467.
authors.forename: Anna
authors.initials: A
authors.lastname: Velcich
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111;
authors.forename: Richard R
authors.initials: RR
authors.lastname: Hardy
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111; Kyoko.Hayakawa@fccc.edu.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hayakawa
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D020397:Goblet Cells / Q000276:immunology* / Q000473:pathology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D055262:Mucin-2 / Q000235:genetics / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D022142:Secretory Vesicles / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology
chemical_list: D001323:Autoantibodies; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; C524626:Muc2 protein, mouse; D055262:Mucin-2; D011947:Receptors, Antigen, B-Cell