In Utero Lymphotoxin Signalling Is Required for Mucosal B Cell Function in Adults

Lymphotoxin-beta Receptor (LTβR) signalling is required for development of secondary lymphoid organs, including Peyer’s patches. Serum IgA levels are also severely reduced in LT-deficient mice. While it has been shown that B cell migration to the lamina propria is impaired in LT-deficient mice, it is unknown whether LTβR signalling affects mucosal B cell function. Here we show that expression of LTαβ ligand on hemapoietic cells was dispensable for induction and maintanence of gut B cell response against a mucosal rotavirus infection in mice where LTβR signaling was intact in utero. However, expression of LTαβ ligand on hemapoietic cells was required for optimal mucosal B cell responses in mice where LTβR signaling was absent in utero. Specifically, compared to WT→WT chimeras, AID induction in mucosal B cells was impaired in WT→LTβ^-/- chimeric mice concomitant with reduced global fecal IgA levels as well as weaker, slower and non-persistent fecal anti-rotavirus IgA responses. Furthermore, mice treated in utero with LTβR inhibitors also exhibited attenuated mucosal anti-rotavirus responses and alterations in gut resident stromal cells in adulthood. Thus, in utero LTβR signaling shapes gut stromal cell populations and has an impact on mucosal B cell function in adult mice.