Papel de BAMBI en la regulación de la respuesta inmune humoral
- AUGUSTÍN RODRÍGUEZ, JUAN JESÚS
- Ramón Merino Pérez Doktorvater/Doktormutter
- Jesús Merino Pérez Co-Doktorvater/Doktormutter
Universität der Verteidigung: Universidad de Cantabria
Fecha de defensa: 16 von Juni von 2017
- Antonio de la Hera Martínez Präsident/in
- Marcos López Hoyos Sekretär/in
- José Ignacio Rodríguez Barbosa Vocal
Art: Dissertation
Zusammenfassung
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.