Article

Elimination of maternally transmitted autoantibodies prevents diabetes in nonobese diabetic mice.

Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Nature Medicine (impact factor: 22.46). 05/2002; 8(4):399-402. DOI:10.1038/nm0402-399 pp.399-402
Source: PubMed

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 beta cell-reactive autoantibodies in prediabetic nonobese diabetic (NOD) mice, 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 beta cells in NOD mice. It will be important to definitively determine whether the transmission of maternal autoantibodies in humans affects diabetes progression in susceptible offspring.

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Keywords

autoimmune diabetes mellitus
 
autoreactive specificities
 
B cell-deficient NOD mothers
 
complementary approach
 
critical environmental parameter influencing
 
diabetes progression
 
genetically susceptible human progeny
 
islet beta cell-reactive autoantibodies
 
islet beta cells
 
maternal autoantibodies
 
maternal B-cell repertoire
 
maternal immunoglobulins
 
maternal transmission
 
non-autoimmune strain
 
prediabetic nonobese diabetic
 
pseudopregnant mothers
 
spontaneous diabetes
 
susceptible offspring
 
T cell-mediated destruction
 
three groups