Gestational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin Disrupts B-Cell Lymphopoiesis and Exacerbates Autoimmune Disease in 24-Week-Old SNF1 Mice

Female SNF1 hybrid mice spontaneously develop an immune complex–mediated glomerulonephritis as early as 24 weeks of age, whereas the disease onset in males is much slower. Further, a rise in concentration of glomerulus-specific autoantibodies via autor-eactive B cells is critical to progression of the disease in this strain. Environmental factors contributing to the onset or degree of such autoimmunity are of interest yet poorly understood. In the present study, time-pregnant SWR 3 NZB dams (10/treatment) were gavaged on gestational 12 with 40 or 80 mg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and the SNF1 offspring were evaluated at 24 weeks of age. Bone marrow B220low-CD242AA4.11 committed B lineage progenitors were increased in female offspring by TCDD, however, committed progenitors and pro-B cells were decreased in males. Splenic marginal zone B cells (CD21hiCD24low2int) were decreased and follicular B cell