title: TIM-1 signaling in B cells regulates antibody production.
abstract: Members of the T cell Ig and mucin (TIM) family have recently been implicated in the control of T cell-mediated immune responses. In this study, we found TIM-1 expression on anti-IgM- or anti-CD40-stimulated splenic B cells, which was further up-regulated by the combination of anti-IgM and anti-CD40 Abs. On the other hand, TIM-1 ligand was constitutively expressed on B cells and inducible on anti-CD3(+) anti-CD28-stimulated CD4(+) T cells. In vitro stimulation of activated B cells by anti-TIM-1 mAb enhanced proliferation and expression of a plasma cell marker syndecan-1 (CD138). We further examined the effect of TIM-1 signaling on antibody production in vitro and in vivo. Higher levels of IgG2b and IgG3 secretion were detected in the culture supernatants of the anti-TIM-1-stimulated B cells as compared with the control IgG-stimulated B cells. When immunized with T-independent antigen TNP-Ficoll, TNP-specific IgG1, IgG2b, and IgG3 Abs were slightly increased in the anti-TIM-1-treated mice. When immunized with T-dependent antigen OVA, serum levels of OVA-specific IgG2b, IgG3, and IgE Abs were significantly increased in the anti-TIM-1-treated mice as compared with the control IgG-treated mice. These results suggest that TIM-1 signaling in B cells augments antibody production by enhancing B cell proliferation and differentiation.
authors.affiliation: Department of Immunology, Juntendo University, 2-1-1 Hongo, Tokyo 113-8421, Japan.
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Usui
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Norihiro
authors.initials: N
authors.lastname: Harada
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Hisaya
authors.initials: H
authors.lastname: Akiba
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D007074:Immunoglobulin G / Q000096:biosynthesis; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D007074:Immunoglobulin G; D008565:Membrane Proteins