Activation of the MEK-ERK Pathway Is Necessary but Not Sufficient for Breaking Central B Cell Tolerance.

ABSTRACT: Newly generated bone marrow B cells are positively selected into the peripheral lymphoid tissue only when they express a B cell receptor (BCR) that is nonautoreactive or one that binds self-antigen with only minimal avidity. This positive selection process, moreover, is critically contingent on the ligand-independent tonic signals transduced by the BCR. We have previously shown that when autoreactive B cells express an active form of the rat sarcoma (RAS) oncogene, they upregulate the receptor for the B cell activating factor (BAFFR) and undergo differentiation in vitro and positive selection into the spleen in vivo, overcoming central tolerance. Based on the in vitro use of pharmacologic inhibitors, we further showed that this cell differentiation process is critically dependent on the ac

SUBMITTER: Greaves SA 

PROVIDER: S-EPMC5900439 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature