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Infection and Immunity, December 2003, p. 6808-6819, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6808-6819.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Characterization and Development of T-Cell Immune Responses in B-Cell-Deficient (Igh-6-/-) Mice with Salmonella enterica Serovar TyphimuriumInfection

Sanja Ugrinovic, Nathalie Ménager, Natalie Goh, and Pietro Mastroeni*

Centre for Veterinary Science, University of Cambridge, Cambridge CB3 0ES, United Kingdom

Received 27 March 2003/ Returned for modification 4 June 2003/ Accepted 2 September 2003

Infection of mice with Salmonella enterica serovar Typhimurium induces strong Th1 T-cell responses that are central to the control of the infection. In the present study, we examined the role of B cells in the development of Th1 T-cell responses to Salmonella by using gene-targeted B-cell-deficient mice (Igh-6-/- mice). The development of Th1 T-cell responses in Igh-6-/- mice was impaired in the early stage of a primary infection. This impairment persisted throughout the course of the disease. The ability of T cells to produce the Th1 cytokine gamma interferon and the frequency at which they did so were lower in Igh-6-/- mice than in control mice. We also observed a transient switch toward Th2 cytokine production in Igh-6-/- mice. Thus, B cells are important for the induction of protective Th1 T-cell responses in the early phase of a Salmonella infection. Activated B cells express high levels of major histocompatibility complex and costimulatory molecules and are nearly as effective as dendritic cells in their antigen-presenting cell (APC) activity. However, their importance as APCs in infection and their role in initiating and/or maintaining T-cell responses are unknown. Here, we show that B cells upregulate costimulatory molecules upon in vitro stimulation with S. enterica serovar Typhimurium and that they can present Salmonella antigens to Salmonella-specific CD4+ T cells. Our results show that B cells are important for the development of T-cell responses in the early stage of a Salmonella infection and that this property may be due to their ability to present antigens to T cells.

* Corresponding author. Mailing address: Centre for Veterinary Science, Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Rd., Cambridge CB3 0ES, United Kingdom. Phone: 44 1223 765 800. Fax: 44 1223 337610. E-mail: pm274{at}cam.ac.uk.

Editor: F. C. Fang

Infection and Immunity, December 2003, p. 6808-6819, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.6808-6819.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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