Faculty Research 1990 - 1999

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.

Document Type

Article

Publication Date

1996

Keywords

Animal, Antigen-Presenting-Cells: im, B-Lymphocytes: im, Diabetes-Mellitus-Insulin-Dependent: et, ge, Genetic-Markers, Homozygote, Immunoglobulins-mu-Chain: ge, im, Linkage-(Genetics), Lymphocyte-Subsets, Mice, Mice-Inbred-NOD, Mice-Mutant-Strains, Spleen: im, cy, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes: im

JAX Source

J Exp Med 1996 Nov 1;184(5):2049-53

Grant

DK46266/DK/NIDDK, DK51090/DK/NIDDK, DK36175/DK/NIDDK

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.