RAPID ELIMINATION OF MATURE AUTOREACTIVE B-CELLS DEMONSTRATED BY CRE-INDUCED CHANGE IN B-CELL ANTIGEN RECEPTOR SPECIFICITY IN-VIVO

Developing autoreactive B cells edit their B cell antigen receptor (EC R) in the bone marrow and are clonally deleted when they fail to reexp ress an innocent BCR, Here, inducible Cre-loxP-mediated gene inversion is used to change the specificity of the BCR on mature IgM(+) IgD(+) B cells in vivo to address the fate of lymphocytes encountering self-a ntigens at this developmental stage. Expression of an autoreactive BCR on mature B cells leads to their rapid elimination from the periphery , a process that is inhibited by constitutive bcl-2 transgene expressi on in an antigen dose-dependent manner. Thus, selection of mature B ce lls into the long-lived peripheral pool does not prevent their deletio n upon encounter of self-antigens.