Persistence of partially functional double-stranded (ds) DNA binding B cells in mice transgenic for the IgM heavy chain of an anti-dsDNA antibody

One mechanism by which anti-double stranded (ds) DNA B cells are regulated is anergy. Multiple phenotypes have been attributed to anergic B cells in various transgenic models. Differences in the nature of the antigen and in the avidity of antigen-antibody interactions may account for these variations in phenotype. In the present study we describe a population of dsDNA binding B cells that display many of the features of anergic B cells, but have characteristics which suggest they are partially functional as well. These B cells do not spontaneously secrete antibody nor can they be induced to secrete antibody following receptor cross-linking in vitro. Furthermore, they display an immature phenotype and have a shortened lifespan, characteristic of anergic B cells. However, they can be induced to secrete anti-dsDNA antibody following activation with T cell-derived factors as well as with lipopolysaccharide (LPS) and they can be recovered by somatic cell hybridization even in the absence of LPS stimulation prior to fusion. These results suggest that antigen receptor signaling can be uncoupled from signaling induced by T cell-derived factors or LPS and that this may be a mechanism for maintaining tolerance. This may have protective advantages because it may enable B cells to be down-regulated in response to autoantigen yet be available for recruitment in an inflammatory response.