Receptor editing in self-reactive bone marrow B cells.
A central paradigm of immunology is clonal selection: lymphocytes displaying clonally distributed antigen receptors are generated and subsequently selected by antigen for growth or elimination. Here we show that in mice transgenic for anti-H-2Kk,b antibody genes, in which a homogeneous clone of developing B cells can be analyzed for the outcome of autoantigen encounter, surface immunoglobulin M+/idiotype+ immature B cells binding to self-antigens in the bone marrow are induced to alter the specificity of their antigen receptors. Transgenic bone marrow B cells encountering membrane-bound Kb or Kk proteins modify their receptors by expressing the V(D)J recombinase activator genes and assembling endogenously encoded immunoglobulin light chain variable genes. This (auto)antigen-directed change in the specificity of newly generated lymphocytes is termed receptor editing.
Tiegs
S L
SL
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
Russell
D M
DM
Nemazee
D
D
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D001854:Bone Marrow Cells; D004277:DNA, Single-Stranded; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D016654:Genes, RAG-1; D006183:H-2 Antigens / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*
D001324:Autoantigens; D004277:DNA, Single-Stranded; D006183:H-2 Antigens; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell