BAMBI is a negative regulator of humoral immune responses.

Abstract

Abstract BAMBI (Bone Morphogenetic Protein and Activin Membrane Bound Inhibitor) is a plasma membrane-associated negative regulator of TGFβ signaling. Using mice deficient in BAMBI and anti-BAMBI monoclonal antibodies, we have recently demonstrated the contribution of this TGFβ inhibitor to the regulation of CD4 T-cell differentiation into pathogenic TH17 cells and tolerogenic regulatory T cells. In the present study, we explored the possible involvement of BAMBI in the control of humoral immune responses. We demonstrated that BAMBI-KO mice developed increased antibody responses against T-independent antigens. In addition, these mutant mice also exhibited enhanced antibody responses against several T-dependent antigens administered by different routes and even in the absence of adjuvants. Using adoptive CD4 T-cell transfer experiments and double WT/BAMBI-KO bone marrow chimeric mice we showed that in the mutant mice, B cells exhibited intrinsic defects that improved their interaction with antigen-specific activated CD4 T cells and their subsequent activation and differentiation into germinal center B cells and antibody secreting cells. In fact, B cells from BAMBI-KO mice exhibited enhanced proliferative responses in vitro and expressed higher levels of surface molecules involved in CD4:B cell interactions. Finally, we demonstrated here that the enhanced T-dependent antibody responses observed in BAMBI-KO mice were reverted after long-term treatment with an anti-TGFβ monoclonal antibody. In conclusion, our present study described for the first time a negative role of BAMBI in the control of T-independent and Tdependent antibody responses through the regulation of TGFβ signaling.