Ligand-independent activity of the B cell antigen receptor in physiology and pathology.
The B cell receptor (BCR) is required for stimulation of B cells by antigen, and is also involved in the negative selection of autoreactive B cells. In the past few years, a constitutive ligand-independent signaling activity of the BCR has been demonstrated. In this paper, the various findings are summarized and their interpretation and their significance, both in pathology and in physiology discussed. The constitutive activity of the BCR may be important for tumor formation, at least in the case of heavy-chain diseases, neoplastic proliferations developed from B cells. A large body of evidence suggests that this activity could be required for B cell survival and would play a role in B cell development as a process monitoring BCR functionality. A model explaining signaling in the absence of antigen as a function of dimer formation is proposed. The putative constitutive activity of the pre-BCR is also discussed.
Corcos
Daniel
D
The Babraham Institute, Babraham, Cambridge, CB22 3AT 4AT, UK. daniel.corcos@bbsrc.ac.uk
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006362:Heavy Chain Disease / Q000235:genetics / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D015448:Leukemia, B-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D007143:Immunoglobulin Heavy Chains; D008024:Ligands; D011947:Receptors, Antigen, B-Cell