Nature Medicine
8, 399 - 402 (2002)
doi:10.1038/nm0402-399
Elimination of maternally transmitted autoantibodies prevents diabetes in nonobese diabetic miceSiri Atma W. Greeley1, Makoto Katsumata2, Liping Yu3, George S. Eisenbarth3, Daniel J. Moore1, Heidi Goodarzi1, Clyde F. Barker1, Ali Naji1
& Hooman Noorchashm11
Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
2
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
3
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado, USA
Correspondence should be addressed to Ali Naji ali.naji@uphs.upenn.eduThe influence of maternally transmitted immunoglobulins on the development of autoimmune diabetes mellitus in genetically susceptible human progeny remains unknown. Given the presence of islet  cell−reactive autoantibodies in prediabetic nonobese diabetic (NOD) mice1,
2, we abrogated the maternal transmission of such antibodies in order to assess their influence on the susceptibility of progeny to diabetes. First, we used B cell−deficient NOD mothers to eliminate the transmission of maternal immunoglobulins. In a complementary approach, we used immunoglobulin transgenic NOD mothers to exclude autoreactive specificities from the maternal B-cell repertoire. Finally, we implanted NOD embryos in pseudopregnant mothers of a non-autoimmune strain. The NOD progeny in all three groups were protected from spontaneous diabetes. These findings demonstrate that the maternal transmission of antibodies is a critical environmental parameter influencing the ontogeny of T cell-mediated destruction of islet cells in NOD mice3. It will be important to definitively determine whether the transmission of maternal autoantibodies in humans4,
5,
6,
7,
8 affects diabetes progression in susceptible offspring.
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