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.

TLDR

In the NOD mouse model, T lymphocytes destroy pancreatic beta cells, but the specific antigen‑presenting cell subsets driving this process remain undefined. The study aimed to determine whether B lymphocytes are required for initiating autoimmune diabetes in NOD mice. This was achieved by generating a speed congenic NOD.Ig mu null line lacking B cells but retaining diabetes susceptibility loci. B cell‑deficient NOD.Ig mu null mice remained diabetes‑free despite normal T‑cell counts, whereas B‑cell‑intact segregants displayed typical disease incidence, indicating B cells are essential for initiating beta‑cell autoimmunity.

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.