Activation of Ras overcomes B-cell tolerance to promote differentiation of autoreactive B cells and production of autoantibodies.

ABSTRACT: Newly generated immature B cells are selected to enter the peripheral mature B-cell pool only if they do not bind (or bind limited amount of) self-antigen. We previously suggested that this selection relies on basal extracellular signal-regulated kinase (Erk) activation mediated by tonic B-cell antigen receptor (BCR) signaling and that this signal can be replaced by an active rat sarcoma (Ras), which are small GTPase proteins. In this study we compared the activity of Ras and Erk in nonautoreactive and autoreactive immature B cells and investigated whether activation of Ras can break tolerance. Our results demonstrate lower levels of active Erk and Ras in autoreactive immature B cells, although this is evident only when these cells display medium/high avidity for self-antigen. Basal activa

SUBMITTER: Teodorovic LS 

PROVIDER: S-EPMC4103347 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature