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.
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.
Serreze
D V
DV
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Chapman
H D
HD
Varnum
D S
DS
Hanson
M S
MS
Reifsnyder
P C
PC
Richard
S D
SD
Fleming
S A
SA
Leiter
E H
EH
Shultz
L D
LD
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*
D005819:Genetic Markers; D007148:Immunoglobulin mu-Chains