CD2-CD48 INTERACTION PREVENTS APOPTOSIS IN MURINE B-LYMPHOCYTES BY UP-REGULATING BCL-2 EXPRESSION

Antigen receptor engagement initiates clonal expansion and antibody se cretion in B lymphocytes in response to foreign antigens. However, bin ding of self antigen to antigen receptors targets self-reactive B cell clones for elimination or inactivation. The antigen-triggered biochem ical events and the eventual response of the cells are dependent on th e simultaneous occupancy of co-stimulatory receptors. CD2 is an interc ellular adhesion molecule implicated in cell activation and expressed in human T and natural killer cells as well as in mouse B lymphocytes. Mouse B cells specific for allogeneic major histocompatibility comple x (MHC) class I initiate a suicide program that leads to DNA fragmenta tion and cell death when confronted with soluble MHC class I while und ergoing clonal expansion when the antigen is present on mitomycin C-tr eated cells. Here we show that occupancy of CD2 in mouse B cells by th e presence of either monoclonal antibody (mAb) specific for CD2, or so luble recombinant mouse CD48, its natural ligand in mouse, prevents th e induction of apoptosis. Furthermore, the in vitro activation by mito mycin C-treated allogeneic cells, is abrogated in the presence of anti -CD48 mAb (OX78). These results indicate that a CD2-CD48 interaction i s involved in the control of B cell activation.