MONOCLONAL, NATURAL ANTIBODIES PREVENT DEVELOPMENT OF DIABETES IN THE NONOBESE DIABETIC (NOD) MOUSE

The development of diabetes in the non-obese diabetic (NOD) mouse is mediated by T cells of both the CD4+CD8- and CD4-CD8+ phenotypes, while B cells are not involved in the effector stage of the disease. We have recently found, however, that treatments with heterologous, polyclonal immunoglobulin (Ig) preparations, as well as suppressing the developing B cell repertoire for the first 4 weeks of life dramatically reduce the incidence of disease and the severity of insulitis, in treated mice. We have further investigated the influence of Igs on the development of autoimmunity by testing the effect of polyclonal mouse-Ig or monoclonal, natural antibodies derived from normal, neonatal BALB c mice. We found that repeated administration of high doses of polyclonal Ig (of xenogenic or isogenic origin), given at birth, inhibits the development of insulitis, as well as diabetes. Furthermore, single injections of moderate doses of isogenic, natural monoclonal antibodies (mAb) administered at the same age, while failing to significantly alter the degree of insulitis, efficiently prevent the development of disease. The effect of mAbs was found to be related to V-region specificity, as only some mAbs of a given isotype and origin had the observed effect. © 1991.