The overall goal of the laboratory is to study B cell development during fetal and adult life. The first B lineage cells emerge in the embryo, and recent studies have demonstrated that these arise from a B lineage progenitor whose developmental potential is restricted to the production of B-1 B cells. B-1 B cells are a minor population of B lymphocytes that are involved in innate immune responses. B cell progenitors that derive from hematopoietic stem cells, and which are destined to produce B-2 B cells, arise subsequently during embryogenesis. B-2 B cells comprise the majority of B cells in the peripheral lymphoid organs and take part in adaptive immune responses. The production of B-2 B cells occurs in the bone marrow throughout life. One aim of the laboratory is to characterize the fetal wave of B cell development in which B-1 B cell progenitors are generated. Emerging data indicate that the transcriptional and microenvironmental regulation of B-1 B cell development is distinct from B-2 B cell differentiation, and a major goal is to compare and contrast these two waves of B lymphopoiesis. Additional work in the laboratory has demonstrated that B-2 B cell development in the bone marrow is reduced with age, and ongoing studies are aimed at defining the microenvironmental and cell intrinsic events that underlie this decline.