Papel de BAMBI en la regulación de la respuesta inmune humoral

Laburpena

We have studied the potential role of BAMBI (BMP and activin membrane bound inhibitor), an inhibitor of TGF, BMPs and activin signaling, in the regulation of the humoral immune responses. BAMBI is expressed at low levels in B lymphocytes at steady state and its expression increases after activation. Using BAMBI knock-out (KO) mice, we have observed that BAMBI deficiency does not affect the development of B cells in the bone marrow, although it promotes an increase in T2 B, memory B, and B-1 subpopulations in the spleen. BAMBI-KO mice show increased production of antibodies against T-independent and T-dependent antigens in different immunization contexts, in correlation with the expansion of all lymphoid populations involved in humoral response (follicular T cells and germinal center B cells). This phenomenon is secondary to an intrinsic B-cell defect, which have a higher expression of surface molecules involved in T-B cell interaction and activation and greater proliferative responses in vitro. The augmented humoral response observed in BAMBI-KO mice is selectively due to an increase in TGFβ signaling through TAK1. The enhanced humoral responses observed in BAMBI-KO mice after vaccination are not accompanied by the spontaneous development of autoantibody-dependent autoimmune pathologies.