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 (Sfbl) of Streptococcus pyogenes can act as an adjuvant for mucosal-delivered antigens (Medina, E., Talay, S. R., Chhatwal, G, S, and Guzman, C, A, 1998, fur. J. Immunol. 28:1069), To characterize the underlying mechanism of the adjuvancity, we investigated the in vitro stimulating activity of Sfbl, The Sfbl 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. Sfbl also induced Ig production by B cells in a T cell-independent manner. The kinetics of Ig isotype accumulation in supernatant fluids and the analysis of Ig-secreting cells suggested that Sfbl 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 Sfbl showed that the fibronectin-binding repeats were responsible for B cell activation. The sera from mice immunized by the intranasal route with Sfbl did not react with either double-stranded DNA, cardiolipin or collagen. Interestingly, stimulation with Sfbl also resulted in the up-regulation of MHC class II molecules expression by B cells and macrophages, The elucidation of the underlying molecular events to the immunomodulatory effect exerted by Sfbl will facilitate the exploitation of the potential of this molecule for the generation of mucosal vaccines.