Igh-6−/−(B-Cell-Deficient) Mice Fail To Mount Solid Acquired Resistance to Oral Challenge with VirulentSalmonella entericaSerovar Typhimurium and Show Impaired Th1 T-Cell Responses toSalmonellaAntigens

ABSTRACTIn the present study we evaluated the role of B cells in acquired immunity toSalmonellainfection by using gene-targeted B-cell-deficient innately susceptible mice on a C57BL/6 background (Igh-6−/−).Igh-6−/−mice immunized with a live, attenuatedaroA Salmonella entericaserovar Typhimurium vaccine strain showed impaired long-term acquired resistance against the virulent serovar Typhimurium strain C5.Igh-6−/−mice were able to control a primary infection and to clear the inoculum from the reticuloendothelial system. However,Igh-6−/−mice, unlikeIgh-6+/+C57BL/6 controls, did not survive an oral challenge with strain C5 at 4 months after vaccination. Transfer of immune serum did not restore resistance inIgh-6−/−mice. Total splenocytes and purified CD4+T cells obtained fromIgh-6−/−mice 4 months after vaccination showed reduced ability to release Th1-type cytokines (interleukin 2 and gamma interferon) upon in vitro restimulation with serovar Typhimurium soluble cell extracts compared to cells obtained fromIgh-6+/+C57BL/6 control mice. Therefore, the impaired resistance to oral challenge with virulent serovar Typhimurium observed in B-cell-deficient mice, which cannot be restored by passive transfer ofSalmonella-immune serum, may be in part due to a reduced serovar Typhimurium-specific T-cell response following primary immunization.