title: The enlarged population of marginal zone/CD1d(high) B lymphocytes in nonobese diabetic mice maps to diabetes susceptibility region Idd11.
abstract: The NOD mouse is an important experimental model for human type 1 diabetes. T cells are central to NOD pathogenesis, and their function in the autoimmune process of diabetes has been well studied. In contrast, although recognized as important players in disease induction, the role of B cells is not clearly understood. In this study we characterize different subpopulations of B cells and demonstrate that marginal zone (MZ) B cells are expanded 2- to 3-fold in NOD mice compared with nondiabetic C57BL/6 (B6) mice. The NOD MZ B cells displayed a normal surface marker profile and localized to the MZ region in the NOD spleen. Moreover, the MZ B cell population developed early during the ontogeny of NOD mice. By 3 wk of age, around the time when autoreactive T cells are first activated, a significant MZ B cell population of adult phenotype was found in NOD, but not B6, mice. Using an F2(B6 x NOD) cross in a genome-wide scan, we map the control of this trait to a region on chromosome 4 (logarithm of odds score, 4.4) which includes the Idd11 and Idd9 diabetes susceptibility loci, supporting the hypothesis that this B cell trait is related to the development of diabetes in the NOD mouse.
authors.affiliation: Section for Immunology, Lund University, Lund, Sweden.
authors.forename: Julia
authors.initials: J
authors.lastname: Rolf
authors.forename: Vinicius
authors.initials: V
authors.lastname: Motta
authors.forename: Nadia
authors.initials: N
authors.lastname: Duarte
authors.forename: Marie
authors.initials: M
authors.lastname: Lundholm
authors.forename: Emma
authors.initials: E
authors.lastname: Berntman
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Bergman
authors.forename: Lydia
authors.initials: L
authors.lastname: Sorokin
authors.forename: Susanna L
authors.initials: SL
authors.lastname: Cardell
authors.forename: Dan
authors.initials: D
authors.lastname: Holmberg
mesh_terms: D000367:Age Factors; D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD / Q000235:genetics* / Q000276:immunology*; D010641:Phenotype; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human