Elimination of maternally transmitted autoantibodies prevents diabetes in nonobese diabetic mice.
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.
Greeley
Siri Atma W
SA
Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Katsumata
Makoto
M
Yu
Liping
L
Eisenbarth
George S
GS
Moore
Daniel J
DJ
Goodarzi
Heidi
H
Barker
Clyde F
CF
Naji
Ali
A
Noorchashm
Hooman
H
D000818:Animals; D001323:Autoantibodies / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D011247:Pregnancy
D001323:Autoantibodies; D007136:Immunoglobulins; C024211:islet cell antibody