The Lymphotoxin LTα₁β₂ Controls Postnatal and Adult Spleen Marginal Sinus Vascular Structure and Function

The lymphotoxin LTα₁β₂ supports the development and maintenance of several aspects of spleen structure, but its significance for marginal sinus (MS) vascular organization is unclear. We showed here that, in early postnatal lymphotoxin-deficient mice, the developing Flk-1⁺ white pulp vessels failed to organize or upregulate MAdCAM-1, leading to altered spatial rearrangement of both the white pulp endothelial cells and the smooth muscle actin-expressing cells. In vitro, MAdCAM-1 directed the reorganization of LTβ receptor⁺ endothelial cells grown on Matrigel. LTα₁β₂ also regulated the maintenance of both MAdCAM-1 expression and mature MS structure in adult mice, contributing importantly to normal trafficking of CD11b⁺ cells in response to bacterial antigens. Together, our studies demonstrate that LTα₁β₂ and LTβ receptor signals control proper development and maintenance of the mature MS structure and implicate MAdCAM-1 in the structuring of the MS endothelial cells that is important for the movement of immune cells within the spleen.