The production of humoral immune responses is dependent on antibody-producing B-cells which develop from precusor stem cells that are present in the bone marrow. Antigen-independent B-cell differentiation involves a series of developmental stages (generally designated as pre-B cell stages) during which a sequential and ordered recombination of antibody genes occurs. Although the stages of pre-B cell differentiation have been fairly well characterized, the control signals that regulate the progressive steps of pre-B cell maturation are not yet understood. We have previously proposed that DNA recombination might play a role in the initiation of lambda gene recombination in maturing pre-B cells. We now propose to directly test this hypothesis by producing mice carrying a mutation that prevents the recombination of RS DNA. We will determine the physiological effect of this RS mutation on B-cell maturation. The results from this project have the potential to have a major impact upon our understanding of the events which occur in the formation of active antibodies in mammals.
