A critical role for lymphotoxin-beta receptor in the development of diabetes in nonobese diabetic mice

To assess the role of lymphotoxin-beta receptor (LT betaR) in diabetes path ogenesis, we expressed an LT betaR-Fc fusion protein in nonobese diabetic ( NOD) mice. The fusion protein was expressed in the embryo, reached high lev els for the first 2 wk after birth, and then declined progressively with ag e. High expression of LT betaR-Fc blocked diabetes development but not insu litis. After the decline in chimeric protein concentration, mice became dia betic with kinetics similar to the controls. Early expression of fusion pro tein resulted in disrupted splenic architecture. However, primary follicles and follicular dendritic cells, but not marginal zones, developed in aged mice. Hence, LT betaR signaling is required for diabetes development and re gulates follicular and marginal zone structures via qualitatively or quanti tatively distinct mechanisms.