Helper T cell-regulated B cell responses constitute a major component of the primary immune response to many pathogens. The subsequent development of antigen-specific immune memory is one critical outcome of this primary adaptive immune response. Antigen-specific immunity develops through a series of intercellular information exchanges organized around cognate T cell receptor-peptide/MHC interactions. Here, we discuss these complex molecularevents andtheircellularconsequences in a serial synapsis model of adaptive immunity. Our laboratory has developed strategies to isolate antigen-specific Th cells and B cells to analyze gene expression and cellular function in single responding lymphocytes directly ex vivo. These studies provide insight into the regulation and cellular organization of antigen-specific immune responses in vivo.