The analysis of B cell differentiation pathways will provide basic information and insights into fundamental questions concerning B cell development, especially the factors that determine the choices made by primary B cells after activation with a multideterminant antigen. My studies will examine the molecular, cellular and physiological outcome of activating primary B cells whose receptors differ in affinity and antigen specificity. The experiments will test the main hypothesis that the consequences of B-Cell receptor (BCR) signaling, particularly with respect to commitment to antibody secretion vs. memory, are influenced by BCR affinity: low affinity B cells are activated to enter the memory but not the antibody secreting pathway, while high affinity B cells are activated to secrete antibodies and also enter the memory phase. These studies are relevant for understanding the B cell differentiation pathway and for human diseases caused by multiple epitope pathogens. The results are applicable to issues of vaccine design for cancer treatment.
