CD2-CD48 interaction prevents apoptosis in murine B lymphocytes by up-regulating bcl-2 expression.
Antigen receptor engagement initiates clonal expansion and antibody secretion in B lymphocytes in response to foreign antigens. However, binding of self antigen to antigen receptors targets self-reactive B cell clones for elimination or inactivation. The antigen-triggered biochemical events and the eventual response of the cells are dependent on the simultaneous occupancy of co-stimulatory receptors. CD2 is an intercellular 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 complex (MHC) class I initiate a suicide program that leads to DNA fragmentation and cell death when confronted with soluble MHC class I while undergoing clonal expansion when the antigen is present on mitomycin C-treated cells. Here we show that occupancy of CD2 in mouse B cells by the presence of either monoclonal antibody (mAb) specific for CD2, or soluble recombinant mouse CD48, its natural ligand in mouse, prevents the induction of apoptosis. Furthermore, the in vitro activation by mitomycin C-treated allogeneic cells, is abrogated in the presence of anti-CD48 mAb (OX78). These results indicate that a CD2-CD48 interaction is involved in the control of B cell activation.
Genaro
A M
AM
Instituto de Bioquimica Facultad de Farmacia, CSIC, Universidad Complutense, Madrid, Spain.
Gonzalo
J A
JA
Bosca
L
L
Martinez
C
C
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000502:physiology*; D018801:CD2 Antigens / Q000502:physiology*; D000071178:CD48 Antigen; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2
D015703:Antigens, CD; D018801:CD2 Antigens; D000071178:CD48 Antigen; C000604065:CD48 protein, human; C000604066:Cd48 protein, mouse; D015395:Histocompatibility Antigens Class I; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2