The aim of the proposed study is the further delineation of B cell differentiation and characterization of B cell triggering in mice. The basic tools in these studies will be antisera specific for the two B cell differentiation markers Lyb3 and Ia.W39 which we have defined previously. Both these antigens are expressed selectively on a functionally defined B lymphocyte subset that is absent in adult mutant mice carrying the xid gene and in newborn normal mice. Since we have previously shown that Lyb3, an isogenic B cell marker, is a receptor for triggering signals, we will now analyze the nature of these signals by studying whether Lyb3 has binding capacity for T cell replacing factor(s). The role of Ia.W39, coded for by a gene in the I-A region of the H-2 complex, as an effector molecule in cell interactions will be tested. In particular, we will examine whether Ia.W39 is essential for optimal presentation of antigens, which are under immune response gene control mapping in the I-A region. Since the membrane expression of both antigens is controlled by a gene on the X-chromosome, there might be a structural or organizational relationship between the two molecules: We will analyze their chronologic appearance during ontogeny. Further we will attempt to in vivo and/or in vitro modulate their expression in order to test whether there is a mutual interdependence in the mechanism of surface expression. We will also study whether a selective loss of receptor/effector function (see above) is seen in these manipulated B cells. We will try to produce hybridomas secreting monoclonal anti-Lyb3 and anti-Ia.W39 antibodies.
Showing the most recent 10 out of 40 publications
