title: Antigen-specific suppression of humoral immunity by anergic Ars/A1 B cells.
abstract: Autoreactive anergic B lymphocytes are considered to be dangerous because of their potential for activation and recruitment into autoimmune responses. However, they persist for days and constitute ∼5% of the B cell pool. We assessed their functional potential in the Ars/A1 transgene model, where anergic B cells express a dual-reactive Ag receptor that binds, in addition to a self-Ag, the hapten p-azophenylarsonate (Ars). When Ars/A1 B cells were transferred into adoptive recipients that were immunized with foreign proteins covalently conjugated with Ars, endogenous IgG immune responses to both were selectively and severely diminished, and the development of T helper cells was impaired. Approximately 95% inhibition of the anti-Ars response was attained with ∼4000 transferred Ars/A1 B cells through redundant mechanisms, one of which depended on their expression of MHC class II but not upon secretion of IL-10 or IgM. This Ag-specific suppressive activity implicates the autoreactive anergic B cell as an enforcer of immunological tolerance to self-Ags.
authors.affiliation: Integrated Department of Immunology, National Jewish Health and University of Colorado School of Medicine, Denver, CO 80206, USA.
authors.forename: Katja
authors.initials: K
authors.lastname: Aviszus
authors.forename: Megan K L
authors.initials: MK
authors.lastname: Macleod
authors.forename: Greg A
authors.initials: GA
authors.lastname: Kirchenbaum
authors.forename: Thiago O
authors.initials: TO
authors.lastname: Detanico
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Heiser
authors.forename: James B
authors.initials: JB
authors.lastname: St Clair
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Guo
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Wysocki
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation; D001324:Autoantigens / Q000096:biosynthesis / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis; D007165:Immunosuppression Therapy / Q000379:methods*; D051379:Mice; D057507:Mice, 129 Strain; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D010132:p-Azobenzenearsonate / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D001324:Autoantigens; D018985:Epitopes, B-Lymphocyte; D007074:Immunoglobulin G; D010132:p-Azobenzenearsonate