Maintenance of B cell anergy requires constant antigen receptor occupancy and signaling.
Immunological tolerance can be mediated by anergy, in which self-reactive B cells persist in the periphery yet remain unresponsive to immunogen. Whether anergy is induced after transient exposure to self antigen and is 'remembered' or requires continuous antigen receptor occupancy and transduction of signals remains unclear. We have explored this using an immunoglobulin-transgenic mouse in which B cells were hapten specific (arsonate) yet cross-reacted with a self antigen that induced anergy in vivo. Many features of anergic cells were rapidly reversed after dissociation of self antigen using hapten competition and these cells regained antigen responsiveness. Our findings indicate that continuous binding of antigen and subsequent receptor signaling are essential for the maintenance of anergy.
Gauld
Stephen B
SB
Integrated Department of Immunology, University of Colorado Health Sciences Center and National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Benschop
Robert J
RJ
Merrell
Kevin T
KT
Cambier
John C
JC
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen; D002118:Calcium / Q000378:metabolism; D017635:Clonal Anergy / Q000276:immunology*; D007136:Immunoglobulins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction; D015854:Up-Regulation; D019061:src-Family Kinases / Q000378:metabolism
D015703:Antigens, CD; D001324:Autoantigens; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases; D002118:Calcium