B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: Analysis of a new 'speed congenic' stock of NOD.Igμ(null) mice

Abstract

The T lymphocytes mediating autoimmune destruction of pancreatic β cells in the nonobese diabetic (NOD) mouse of 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)μ allele (Igμ(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.Igμ(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 β cell autoreactive T cells in NOD mice.