The development of immune responses involves, in part, the maturation of a diverse set of B-cells that can produce antibodies against a multitude of foreign antigens. These B-cells arise from stem cells in the bone marrow and pass through a crucial developmental stage, termed the pre-B cell stage, during which each B-cell becomes committed to recognizing a particular antigenic structure. This commitment involves the recombination of the heavy and light chain genes that encode the specific antibody molecule eventually produced by each individual B-cell. The pre-B cell differentiation stage is actually a series of stages, each of which is marked by the recombination of heavy chain, kappa light chain or lambda light chain antibody genes. The regulation of pre-B cell maturation will be studied using a series of Abelson murine leukemia virus transformed cell lines (Abelson lines) that represent various pre-B differentiation stages. The mechanisms of regulation and the molecules involved in regulatory control will be investigated by RNA transcriptional analyses of genes that may be involved in the regulation of development, DNAase I studies on the effect of chromosome structure on Ig gene recombination, gene transfer studies on the effect of antibody proteins on the gene recombination process and mRNA sequencing studies on the accuracy of gene recombination in the Lambda light chain gene system.
