Spleen B cell compartment characterization in different murine genetic backgrounds during a secondary immune response to an immunodominat Trypanosoma cruzi antigen

PELLEGRINI A, GUIÑAZU N, AOKI M, CHICO-CALERO I, CARRERA-SILVA E, GIRONES N, FRESNO M, GEA S.

Buenos Aires, Argentina

Simposio; International Symposium “Molecular Immunology of Protozoan Infections”; 2007

There is increasing interest in the study of roles that B cells may play in regulating immune responses both in protection and pathogenesis. However, little is known about additional immune functions of B cells independently of Ab production. In this study we have assessed in different host genetic backgrounds how the immunization with cruzipain, an immunodominat Trypanosoma cruzi T dependent Ag affect several parameters of B cells during secondary immune responses. We have previously reported that BALB/c immunized with cruzipain, induced heart autoimmunity whereas C57BL/6 mice were resistant. In a comparative study employing the same experimental model, the characterization of B cell compartment revealed that germinal centers (GC) and plasma cell populations were increased in immune BALB/c compared to B6 mice, result observed at 14 days upon last immunization. We showed that enriched B cells from Cz immune BALB/c mice had higher ability to proliferate to specific and unspecific stimuli respect to B cells from Cz immune B6 mice. Additionally, we found that the cytokines produced by enriched B cells was critically influenced by the balance of cytokines induced in vivo. Notably, only enriched spleen B cells from BALB/c mice produced IL-4 in vitro with or without Ag stimulation. The analysis of MHC-II, CD40, CD86 activation surface markers showed higher expression of these molecules on B cells from Cz immune BALB/c mice. Through the employment of IL-4 or IFN-gR KO mice in this model, we provided evidence supporting the differential effect of these cytokine signals in MHC-II and CD86 expression on B cells. These findings demonstrate the influence of genetic background on B cell activation and emphasize the importance of examining B cells behaviour in the context of the specific backgrounds and immunogens. Establishing of experimental models would be extremely helpful for studying the development and progression of disease and the immunophatology of the Chagas’ disease.