Search

Abstract Introduction  B lymphocytes remain in a resting state until activated by antigenic stimuli through interaction with the B cell receptor (BCR). Coreceptors on B cells can modulate the thresholds for signaling through the BCR for growth and differentiation. CD72 is a B cell coreceptor that has been shown to interact with CD100, a semaphorin, and to enhance BCR signaling. Discussion  CD72 ligation induces a variety of early signaling events such as activation of the Src kinases Blk and Lyn and the non-src kinase Btk leading to activation of the mitogen-activated protein (MAP) kinases, events usually associated with positive signaling. CD72 signals can enable Btk-deficient B cells to overcome their unresponsiveness to BCR signaling. On the other hand, BCR-mediated signals are enhanced in CD72-deficient cells but are reduced in CD100 null cells. The dual effects of CD72 on B cells can be explained by its association with positive and negative signaling molecules. Thus, CD72 interacts with SHP-1, an SH2-domain containing protein tyrosine phosphatase, a negative regulator of signaling, and Grb2, an adaptor protein associated with the Ras/MAPK pathway. Ligation of CD72 also triggered its association with CD19, a positive modulator of B cell receptor signaling. We propose a dual signaling hypothesis to explain the growth and differentiation promoting properties of CD72. Deficiency in either CD72 or CD100 leads to autoimmunity in mouse models. CD72 expression and polymorphisms exhibit some association with autoimmune diseases such as lupus, Sjogren’s syndrome, and type 1 diabetes. [ABSTRACT FROM AUTHOR]

A DBA/1 B10.D2-specific monoclonal antibody (CY34) is described which defines a new murine B lymphocyte differentiation antigen designated Lyb-8.2. The ontogeny, strain distribution, and cell-surface density of the antigen were studied by radioimmunoassay and by fluorescence-activated cell sorter (FACS) analysis. Lyb-8.2 appears to be expressed on pre-B cells and on all mature B lymphocytes. Lyb-8.2 molecules immunoprecipitated from surface labeled B10.D2 spleen cells migrated in polyacrylamide gels with an apparent mol. wt. of 95000-105000 daltons and were bound by lentil lectin. The expression of Lyb-8.2 is controlled by a locus on chromosome 7 that is closely linked to Gpi-1 and RP-2. Added Lyb-8.2-specific antibody did not measurably impair B lymphocyte function in several in vitro systems studied. [ABSTRACT FROM AUTHOR]