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.
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.
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D V Serreze, H D Chapman, D S Varnum, M S Hanson, P C Reifsnyder, S D Richard, S A Fleming, E H Leiter, L D Shultz; 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.. J Exp Med 1 November 1996; 184 (5): 2049–2053. doi: https://doi.org/10.1084/jem.184.5.2049
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