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.