The study of the immunobiology of B lymphocytes in this research program has been based on two complementary approaches: 1) the analysis of genetic markers of mouse immunoglobulins and the regulation of their production; and 2) the analysis of B cell heterogeneity, function and activation through the study of mice with genetically determined defects and through the use of immunogenetic techniques to study regulation of clonal expression. New efforts have recently been initiated to prepare monoclonal antibodies to differentiation antigens of B lymphocyte subpopulations and to clone mitogen and antigen reactive B lymphocytes.