title: Tolerant anti-insulin B cells are effective APCs.
abstract: Autoreactive B lymphocytes that are not culled by central tolerance in the bone marrow frequently enter the peripheral repertoire in a state of functional impairment, termed anergy. These cells are recognized as a liability for autoimmunity, but their contribution to disease is not well understood. Insulin-specific 125Tg B cells support T cell-mediated type 1 diabetes in NOD mice, despite being anergic to B cell mitogens and T cell-dependent immunization. Using this model, the potential of anergic, autoreactive B cells to present Ag and activate T cells was investigated. The data show that 1) insulin is captured and rapidly internalized by 125Tg BCRs, 2) these Ag-exposed B cells are competent to activate both experienced and naive CD4(+) T cells, 3) anergic 125Tg B cells are more efficient than naive B cells at activating T cells when Ag is limiting, and 4) 125Tg B cells are competent to generate low-affinity insulin B chain epitopes necessary for activation of diabetogenic anti-insulin BDC12-4.1 T cells, indicating the pathological relevance of anergic B cells in type 1 diabetes. Thus, phenotypically tolerant B cells that are retained in the repertoire may promote autoimmunity by driving activation and expansion of autoaggressive T cells via Ag presentation.
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. peggy.kendall@vanderbilt.edu
authors: Peggy L
authors: PL
authors: Kendall
authors: James B
authors: JB
authors: Case
authors: Allison M
authors: AM
authors: Sullivan
authors: Jeff S
authors: JS
authors: Holderness
authors: K Sam
authors: KS
authors: Wells
authors: Edwin
authors: E
authors: Liu
authors: James W
authors: JW
authors: Thomas
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology*; D018920:Coculture Techniques; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism; D007108:Immune Tolerance; D007330:Insulin Antibodies / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D007330:Insulin Antibodies; D011947:Receptors, Antigen, B-Cell
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