The Spleen and Organized Lymph Nodes Are Not Essential for the Development of Gut-induced Mucosal Immune Responses in Lymphotoxin-alpha Deficient Mice

Lymphotoxin knock-out (KO) mice generate specific immune responses to orally administered immunogens despite having neither gut-associated nor peripheral lymphoid tissues. The spleen, therefore, was expected to play a role in the generation of immune responses in these KO mice. KO and wild-type (wt) mice were splenectomized and orally immunized with Salmonella typhimurium. Splenectomy produced the most profound effects on serum and fecal IgA levels in KO mice. Total and antigen-specific serum and fecal IgA were increased in splenectomized wt mice but decreased in splenectomized KO mice. Antigen-specific serum IgG was decreased in both KO and wt splenectomized mice while total IgG increased in splenectomized wt mice. Both splenectomized wt and KO mice demonstrated a compensatory expansion of the lamina propria compartment characterized by a significant increase in the number of IgA spot-forming cells. KO mice demonstrated further compensation for the loss of the spleen in the accelerated development of ectopic lymphoid tissues. We conclude that the spleen plays a prominent role as a lymphoid organ in KO mice but its removal does not abolish immune responsiveness. Residual immune responsiveness in splenectomized KO mice following oral immunization appears to be due to expansion and/or development of alternate effector compartments.