Ligand-independent tonic signaling in B-cell receptor function.
The random and inherently imprecise process of V(D)J recombination is the foundation for generation of the B-cell receptor (BCR). Signals must be generated to trigger selective processes that retain cells expressing a functional BCR, and these signals must be antigen-independent to insure an unbiased and diverse pool of newly formed B cells. Moreover, BCR expression, and presumably signaling, is essential for the continued survival of the B cell. Although BCR signaling is generally thought to depend upon ligand-induced aggregation, recent studies argue that some aspects of BCR signaling occur independently of antigen, and, furthermore, these non-induced or 'tonic' signals are linked to specific cellular processes operating at multiple stages of B-cell development. The potential co-existence of tonic and induced signaling suggests a unique aspect of BCR complexes, or at least an aspect of receptors that has previously been under-appreciated.
Monroe
John G
JG
University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, Pennsylvania 191104, USA. monroej@mail.med.upenn.edu
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011995:Recombination, Genetic / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D045567:VDJ Recombinases / Q000235:genetics / Q000276:immunology
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; C064655:V(D)J recombination activating protein 2; D045567:VDJ Recombinases