title: Activation-induced deaminase contributes to the antibody-independent role of B cells in the development of autoimmunity.
abstract: B cells contribute to autoimmunity both as secretors of pathogenic antibodies and through the activation of autoreactive T cells. B cells and antibodies acquire higher affinity to self-antigen through a process known as immunoglobulin hypermutation or SHM. The contribution of SHM to pathogenic antibody development in lupus has been established in various autoimmune mouse models and by examining antibodies from patients. However, its role in the antibody-independent contribution of B cells to autoimmunity has not been examined. Herein, we generate lupus-prone MRL/lpr mice with a limited IgM-only B cell repertoire, no secreted antibodies and no SHM. This enabled us to isolate the role of somatic hypermutation in B cell-mediated autoimmunity. We found that SHM-deficiency correlated with a reduction in autoreactive B cells, a decrease in T cell activation and a decrease in kidney lymphocytic infiltration. These data establish AID as an important contributor to the antibody-independent role of B cells in autoimmunity.
authors.affiliation: Somatic Hypermutation Group, Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Chuancang
authors.initials: C
authors.lastname: Jiang
authors.forename: Ming-Lang
authors.initials: ML
authors.lastname: Zhao
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Waters
authors.forename: Marilyn
authors.initials: M
authors.lastname: Diaz
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D003564:Cytidine Deaminase / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D019463:Mice, Inbred MRL lpr; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007075:Immunoglobulin M; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase