Dendritic cells license regulatory B cells to produce IL-10 and mediate suppression of antigen-specific CD8 T cells

Regulatory B cells (Bregs) suppress and reduce autoimmune pathology. However, given the variety of Breg subsets, the role of Bregs in the pathogenesis of type 1 diabetes is still unclear. Here, we dissect this fundamental mechanism. We show that natural protection from type 1 diabetes in nonobese diabetic (NOD) mice is associated with increased numbers of IL-10-producing B cells, while development of type 1 diabetes in NOD mice occurs in animals with compromised IL-10 production by B cells. However, B cells from diabetic mice regain IL-10 function if activated by the innate immune receptor TLR4 and can suppress insulin-specific CD8 T cells in a dendritic cell (DC)-dependent, IL-10-mediated fashion. Suppression of CD8 T cells is reliant on B-cell contact with DCs. This cell contact results in deactivation of DCs, inducing a tolerogenic state, which in turn can regulate pathogenic CD8 T cells. Our findings emphasize the importance of DC–Breg interactions during the development of type 1 diabetes

Lean body mass of well-nourished women is preserved during lactation

To determine whether the lean body mass of well-nourished women was mobilized to support milk protein output during lactation, the body composition of 10 lactating and 10 nonlactating women was examined longitudinally at 6-wk intervals between 6 and 24 wk postpartum and at 52 wk postpartum, and that of 10 nulliparous women was examined at equivalent intervals, by using clinical anthropometry and whole-body potassium counting. Milk production was determined at 6-wk intervals during the period of exclusive breast-feeding (6-24 wk postpartum) by the test-weighing procedure. Milk composition was determined by chemical analysis. Dietary intakes were determined at 6-wk intervals between 6 and 24 wk postpartum from 3-d food records with use of a nutrient database. Lean body mass was maintained in women who exclusively breast-fed their infants during the first 6 mo postpartum while consuming dietary protein in amounts that exceeded those of their nonlactating counterparts by 55%. The high protein intakes were sustained throughout lactation despite a progressive reduction by 32% of milk protein output. Lean body mass was preserved throughout lactation in well-nourished women, suggesting that the metabolic needs of milk protein production were met solely by higher protein intakes of the lactating women.published_or_final_versio