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 (BCR) in the bone marrow and are clonally deleted when they fail to reexpress 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-antigens 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 expression in an antigen dose-dependent manner. Thus, selection of mature B cells into the long-lived peripheral pool does not prevent their deletion upon encounter of self-antigens.
Lam
K P
KP
Institute for Genetics, University of Cologne, Weyertal 121, D-50931 Cologne, Germany.
Rajewsky
K
K
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D007446:Chromosome Inversion; D005803:Genes, Immunoglobulin; D019254:Genes, bcl-2; D007072:Immunoglobulin D / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D019426:Integrases / Q000096:biosynthesis / Q000235:genetics; D008212:Lymphocyte Depletion; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000276:immunology*; D013234:Stem Cells; D014764:Viral Proteins
D007072:Immunoglobulin D; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases