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 lymphocy tes, macrophages, and dendritic cells) contribute to the development a nd activation of diabetogenic T cells in NOD mice. In the current stud y we utilized a functionally inactivated immunoglobulin (Ig)mu allele (Ig mu(null)) to generate a ''speed congenic'' stock of B lymphocyte-d eficient NOD mice that are fixed for linkage markers delineating previ ously identified diabetes susceptibility (Idd) genes. These B lymphocy te 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 unrecog nized role that is essential for the initial development and/or activa tion of beta cell autoreactive T cells in NOD mice.