Abstract
The influence of maternally transmitted immunoglobulins on the development of autoimmune diabetes mellitus in genetically susceptible human progeny remains unknown. Given the presence of islet β 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 β 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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Acknowledgements
We thank H.K. Song, T.H. Lin, L.E. Noto and A. Schlachterman for their helpful discussion and assistance; and J. Ahn, K.W. Greeley and A.J. Reed for critical reading of the manuscript. This work was supported by grants HD37754 and DK54215 from the National Institutes of Health.
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Greeley, S., Katsumata, M., Yu, L. et al. Elimination of maternally transmitted autoantibodies prevents diabetes in nonobese diabetic mice. Nat Med 8, 399–402 (2002). https://doi.org/10.1038/nm0402-399
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DOI: https://doi.org/10.1038/nm0402-399