Autoreactive B cells escape clonal deletion by expressing multiple antigen receptors.

摘要: IgH and L chain transgenes encoding a phosphocholine (PC)-specific Ig receptor were introduced into recombinase-activating gene (Rag-2−/−) knockout mice. The PC-specific B cells that developed behaved like known autoreactive lymphocytes. They 1) developmentally arrested in the bone marrow, 2) unable to secrete Ab, 3) able escape clonal deletion develop B1 peritoneal cavity, 4) rescued by overexpression of bcl-2 . A second IgL was genetically Rag-2−/− mice expressing receptor. These dual chain-expressing had peripheral lymphoid organs coexpressed both anti-PC Ab as well employing available does not generate an Coexpression additional molecules relieved functional anergy anti-PC-specific cells, demonstrated detection circulating anti-PC-Abs. We call this novel mechanism which can persist compromising allelic exclusion dilution. Rescue would be beneficial host because these Abs are vital for protection against pathogens such Streptococcus pneumoniae.