Active PI3K abrogates central tolerance in high-avidity autoreactive B cells.
J Exp Med
; 216(5): 1135-1153, 2019 05 06.
Article
en En
| MEDLINE
| ID: mdl-30948496
ABSTRACT
Autoreactive B cells that bind self-antigen with high avidity in the bone marrow undergo mechanisms of central tolerance that prevent their entry into the peripheral B cell population. These mechanisms are breached in many autoimmune patients, increasing their risk of B cell-mediated autoimmune diseases. Resolving the molecular pathways that can break central B cell tolerance could therefore provide avenues to diminish autoimmunity. Here, we show that B cell-intrinsic expression of a constitutively active form of PI3K-P110α by high-avidity autoreactive B cells of mice completely abrogates central B cell tolerance and further promotes these cells to escape from the bone marrow, differentiate in peripheral tissue, and undergo activation in response to self-antigen. Upon stimulation with T cell help factors, these B cells secrete antibodies in vitro but remain unable to secrete autoantibodies in vivo. Overall, our data demonstrate that activation of the PI3K pathway leads high-avidity autoreactive B cells to breach central, but not late, stages of peripheral tolerance.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Autoantígenos
/
Linfocitos B
/
Autoinmunidad
/
Fosfatidilinositol 3-Quinasa Clase Ia
/
Tolerancia Central
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2019
Tipo del documento:
Article
País de afiliación:
Colombia