B cell clonal elimination induced by membrane-bound self-antigen may require repeated antigen encounter or cell competition.
Transgenic mouse experiments indicate that autoreactive B cells are eliminated upon encounter with membrane self-antigen. In this study we tested how B cell tolerance to MHC class I antigens is affected by altering the frequency of antigen-carrying cells in mixed bone marrow (BM) chimeras. When antigen-bearing cells are present at low frequency, the reactive B cells and their antigens may coexist in the peripheral lymphoid organs, but under these conditions the B cells are functionally anergic and have a shortened lifespan. Such putative anergic cells are strongly deleted in the presence of additional, non-antigen-bearing, non-transgenic B cells. Since the antigen concentration on the surface of each antigen-bearing cell should be high, these results suggest that for efficient deletion of autoreactive B cells multiple antigen encounters may be required, particularly when cellular competition is weak. These results have implications for the therapeutic use of BM chimerism to induce B cell tolerance to grafts.
Lang
J
J
University of Colorado Health Sciences Center, Barbara Davis Center for Juvenile Diabetes, Denver, USA.
Nemazee
D
D
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000276:immunology
D000954:Antigens, Surface; D001324:Autoantigens; D011947:Receptors, Antigen, B-Cell