title: Positive selection of B10 cells is determined by BCR specificity and signaling strength.
abstract: B10 cells, a regulatory B cell subset, negatively regulate immune responses in an IL-10-dependent manner. However, the mechanism of B10 cell development is unclear. We found that B10 cells mainly identified self-antigens. TgVH3B4 transgenic mice, whose VH was derived from an actin-reactive natural antibody, exhibit elevated numbers of actin-binding B10 cells. Immunization of TgVH3B4 mice with actin induced elevated B10 cell numbers in an antigen-specific manner, indicating positive selection of B10 cells by self-antigens. Furthermore, higher BCR signaling strength facilitated B10 cell development. We also observed that actin-reactive IgG levels were unchanged in TgVH3B4 mice after immunization with actin in contrast to the elevated OVA-reactive IgG level after immunization with OVA, indicating that B10 cells acted in an antigen-specific manner to inhibit the immune response. Our data demonstrate for the first time that B10 cells are positively selected by self-reactivity and that higher BCR signaling strength promotes B10 cell development.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
authors.forename: Jigang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wan
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
authors.forename: Jixin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Fu
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China. Electronic address: liwei1@fmmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000199:Actins / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000915:Antibody Affinity; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D060966:Clonal Selection, Antigen-Mediated; D000939:Epitopes / Q000276:immunology / Q000378:metabolism*; D007108:Immune Tolerance; D007114:Immunization; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016753:Interleukin-10 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000199:Actins; D001324:Autoantigens; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell; D016753:Interleukin-10
keywords: Antigen specificity; BCR; Regulatory B cells; Signaling strength