The object of the proposed investigation is to study the antigent-independent and antigen-dependent maturation of B lymphocytes. In the first case, we will study the sequence of events in which immature precursor cells in the bone marrow give rise to mature virgin B cells in the peripheral lymphoid tissues. In the second, we will study the dual pathway of antigen-dependent differentiation which generates antibody forming cells on one hand, and memory B lymphocytes on the other. Parameters used to determine maturation events, and to define B cell populations are cell surface markers (isotype pattern of cell surface immunoglobulin, Ia antigen, etc.), immune function (ability to transfer the adoptive primary and secondary antibody response in vivo and in vitro), and certain physiological characteristics (migration pattern, tissue distribution, cell size, etc.). One of our main goals is to determine the relationship between B cell surface IgD receptors, and the capacity to generate memory B cells. Methods used in these studies include immunofluorescent staining of B cell surface markers, and isolation of purified cell populations using the fluorescence activated cell sorter. The function of the purified cells is tested in adoptive transfer experiments which measure the ability of the cells to generate antibody forming cells and memory B cells. In addition, we are studying the differentiative capacity and immunoglobulin gene context of a spontaneously occurring B lymphocyte tumor of BALB/c mice (BCL1). This tumor bears IgM and IgD on the cell surface, and is stimulated to secrete IgM after incubation in vitro with lipopolysaccharide.