Fibronectin-binding protein I of Streptococcus pyogenes promotes T cell-independent proliferation of murine B lymphocytes and enhances the expression of MHC class II molecules on antigen-presenting cells.
We have previously shown that fibronectin-binding protein I (SfbI) of Streptococcus pyogenes can act as an adjuvant for mucosal-delivered antigens (Medina, E., Talay, S. R., Chhatwal, G. S. and Guzmán, C. A. 1998. Eur. J. Immunol. 28:1069). To characterize the underlying mechanism of the adjuvancity, we investigated the in vitro stimulating activity of SfbI. The SfbI protein promoted a dose-dependent proliferation of mouse spleen cells. Studies performed using cellular subpopulations showed that proliferation involved B cells and was T cell- and macrophage-independent. SfbI also induced lg production by B cells in a T cell-independent manner. The kinetics of lg isotype accumulation in supernatant fluids and the analysis of Ig-secreting cells suggested that SfbI stimulates B cells expressing different Ig isotypes rather than promoting the isotype switching of single subpopulations. Experiments performed with recombinant proteins encompassing different functional domains of SfbI showed that the fibronectin-binding repeats were responsible for B cell activation. The sera from mice immunized by the intranasal route with SfbI did not react with either double-stranded DNA, cardiolipin or collagen. Interestingly, stimulation with Sfbl also resulted in the up-regulation of MHC class 11 molecules expression by B cells and macrophages. The elucidation of the underlying molecular events to the immunomodulatory effect exerted by SfbI will facilitate the exploitation of the potential of this molecule for the generation of mucosal vaccines.
Medina
E
E
Department of Microbial Pahtogenicity and Vaccine Research, GBF-National Research Centre for Biotechnology, Braunschweig, Germany.
Talay
S R
SR
Chhatwal
G S
GS
Guzmán
C A
CA
D018829:Adhesins, Bacterial; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001426:Bacterial Proteins / Q000494:pharmacology*; D002352:Carrier Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D013297:Streptococcus pyogenes; D013601:T-Lymphocytes / Q000276:immunology
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II; C111389:I-Ad antigen; D007132:Immunoglobulin Isotypes; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; C078635:fibronectin-binding proteins, bacterial