B lymphocyte activation is initiated by the binding of antigens to the clonally expressed B cell receptors (BCRs) triggering signaling cascades that lead to the transcription of a variety of genes associated with B cell activation. Provided with the appropriate T cell help and the microenvironment of germinal centers antigen drives B cells to proliferate and differentiate into long-lived plasma cells and memory B cells that together constitute immunological memory. Here I describe efforts in my laboratory to gain an understanding of the cellular and molecular mechanisms that underlie three processes central to B cell biology namely, the initiation of BCR signaling, the interactions of the BCR with the innate immune system Toll-like receptors, and the generation and maintenance of B cell memory. Such knowledge is likely to aid research efforts in two areas of high public health priority, namely, the development of new therapeutics to control B cell responses in autoimmune disease and the design of effective vaccines to control infectious diseases.