This chapter reviews the pertinent findings relating to the factors controlling the growth and differentiation of the single B cell grown as a clone in vitro. It presents findings on the effects of antigenic stimuli, lymphokines, T cells, and other accessory cells on the activation and clonal differentiation of single hapten-specific B cells. The chapter deals with the knowledge generated in single cell cloning systems. It also reviews the developments that led to the generation of those systems. Many of the factors which may influence whether a particular B cell will be activated into the differentiation pathway on interaction with specific antigen have been well identified in the literature. In vitro, limiting dilution cloning methods, where precursor B cells are isolated from many of the effects of the immune network, has provided a most useful approach to the assessment of B cell competence and activation leading to blastogenesis, clonal expansion, and differentiation.