title: B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new "speed congenic" stock of NOD.Ig mu null mice.
abstract: The T lymphocytes mediating autoimmune destruction of pancreatic beta cells in the nonobese diabetic (NOD) mouse model of insulin-dependent diabetes mellitus (IDDM) may be generated due to functional defects in hematopoietically derived antigen-presenting cells (APC). However, it has not been clear which particular subpopulations of APC (B lymphocytes, macrophages, and dendritic cells) contribute to the development and activation of diabetogenic T cells in NOD mice. In the current study we utilized a functionally inactivated immunoglobulin (Ig) mu allele (Ig mu null) to generate a "speed congenic" stock of B lymphocyte-deficient NOD mice that are fixed for linkage markers delineating previously identified diabetes susceptibility (Idd) genes. These B lymphocyte NOD.Ig mu null mice had normal numbers of T cells but were free of overt IDDM and insulitis resistant, while the frequency of disease in the B lymphocyte intact segregants was equivalent to that of standard NOD mice in our colony. Thus, B lymphocytes play a heretofore unrecognized role that is essential for the initial development and/or activation of beta cell autoreactive T cells in NOD mice.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors.forename: D V
authors.initials: DV
authors.lastname: Serreze
authors.forename: H D
authors.initials: HD
authors.lastname: Chapman
authors.forename: D S
authors.initials: DS
authors.lastname: Varnum
authors.forename: M S
authors.initials: MS
authors.lastname: Hanson
authors.forename: P C
authors.initials: PC
authors.lastname: Reifsnyder
authors.forename: S D
authors.initials: SD
authors.lastname: Richard
authors.forename: S A
authors.initials: SA
authors.lastname: Fleming
authors.forename: E H
authors.initials: EH
authors.lastname: Leiter
authors.forename: L D
authors.initials: LD
authors.lastname: Shultz
mesh_terms: D000367:Age Factors; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D008040:Genetic Linkage; D005819:Genetic Markers; D006720:Homozygote; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000276:immunology*; D016131:Lymphocyte Subsets; D051379:Mice; D016688:Mice, Inbred NOD; D008817:Mice, Mutant Strains; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D005819:Genetic Markers; D007148:Immunoglobulin mu-Chains