title: Contribution of the innate immune system to autoimmune diabetes: a role for the CR1/CR2 complement receptors.
abstract: B lymphocytes are required for diabetogenesis in nonobese diabetic (NOD) mice. The complement component of the innate immune system regulates B cell activation and tolerance through complement receptors CR1/CR2. Thus, it is important to assess the contribution of complement receptors to autoimmune diabetes in NOD mice. Examination of the lymphoid compartments of NOD mice revealed striking expansion of a splenic B cell subset with high cell surface expression of CR1/CR2. This subset of B cells exhibited an enhanced C3 binding ability. Importantly, long-term in vivo blockade of C3 binding to CR1/CR2 prevented the emergence of the CR1/CR2(hi) B cells and afforded resistance to autoimmune diabetes in NOD mice. These findings implicate complement as an important regulatory element in controlling the T cell-mediated attack on islet beta cells of NOD mice.
authors.affiliation: Department of Surgery, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
authors.forename: H
authors.initials: H
authors.lastname: Noorchashm
authors.forename: D J
authors.initials: DJ
authors.lastname: Moore
authors.forename: Y K
authors.initials: YK
authors.lastname: Lieu
authors.forename: N
authors.initials: N
authors.lastname: Noorchashm
authors.forename: A
authors.initials: A
authors.lastname: Schlachterman
authors.forename: H K
authors.initials: HK
authors.lastname: Song
authors.forename: C F
authors.initials: CF
authors.lastname: Barker
authors.forename: A
authors.initials: A
authors.lastname: Naji
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D003176:Complement C3 / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D016130:Immunophenotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D017463:Receptors, Complement 3b / Q000276:immunology*; D017464:Receptors, Complement 3d / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D003176:Complement C3; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d