Igh-6(-/-) (B-cell-deficient) mice fail to mount solid acquired resistanceto oral challenge with virulent Salmonella enterica serovar typhimurium and show impaired Th1 T-cell responses to Salmonella antigens

In the present study we evaluated the role of B cells in acquired immunity to Salmonella infection by using gene-targeted B-cell-deficient innately su sceptible mice on a C57BL/6 background (Igh-6(-/-)). Igh-6(-/-) mice immuni zed with a live, attenuated aroA Salmonella enterica serovar Typhimurium va ccine strain showed impaired long-term acquired resistance against the viru lent serovar Typhimurium strain C5. Igh-6(-/-) mice were able to control a primary infection and to clear the inoculum from the reticuloendothelial sy stem. However, Igh-6(-/-) mice, unlike Igh-6(+/+) C57BL/6 controls, did not survive an oral challenge with strain C5 at 4 months after vaccination, Tr ansfer of immune serum did not restore resistance in Igh-6(-/-) mice. Total splenocytes and purified CD4(+) T cells obtained from Igh-6(-/-) mice 4 mo nths after vaccination showed reduced ability to release Th1-type cytokines (interleukin 2 and gamma interferon) upon in vitro restimulation with sero var Typhimurium soluble cell extracts compared to cells obtained from Igh-6 (+/+) C57BL/6 control mice. Therefore, the impaired resistance to oral chal lenge with virulent serovar Typhimurium observed in B-cell-deficient mice, which cannot be restored by passive transfer of Salmonella-immune serum, ma g be in part due to a reduced serovar Typhimurium-specific T-cell response following primary immunization.