The proposed experiments are designed to provide insight into the molecular and cellular basis for humoral (antibody mediated) immunity. Such knowledge is of fundamental importance to the development of effective vaccination strategies, and for approaches to the generation of monoclonal antibodies for use in diagnostic and therapeutic applications. In particular, the experiments will examine how the antibodies expressed by an immune B cell population differ from those expressed by the "naive" population, and whether these two populations differ in their potential for further differentiation. The immune response to the hapten p-azophenylarsonate (Ars) in strain A/j mice will be used as a model system. To directly examine the composition and differentiative capabilities of the Ars-induced immune B cell population in A/j mice, we will exploit the fact that this population can respond to the hapten p-azophenylsulfonate (Sulf), while the "naive" B cell precursors to this immune population cannot. Using this approach, the following questions will be addressed: (1) Do changes in the structure and function of the antibodies expressed by the Ars-induced memory B cell population take place during secondary and higher order immune responses to Sulf? (2) How related in structure to Ars does a "boosting" epitope have to be to elicit an immune response from the Ars-induced immune B cell population? (3) Does the Ars-immune B cell population produce a Sulf-boosted immune response in an irradiated mouse host (radiation chimera) that differs quantitatively of qualitatively from that observed in situ? and (4) Are the Ars-immune B cell population and the B cell population that generates the primary anti-Ars serum antibody response derived from different subpopulations of "naive" B cell precursors?