We propose to study the organization, rearrangement and diversification of antibody heavy chain genes in the mouse during B-cell differentiation. Recombinant DNA techniques will be employed to prepare heavy chain cDNA probes and to construct genomic libraries of undifferentiated (sperm) and differentiated (myeloma, hybridoma, normal B cell) DNAs. Heavy chain genes will be isolated and characterized by restriction enzyme mapping, heteroduplex analyses, and DNA sequencing. We are interested in characterizing the DNA rearrangements to occur during B-cell differentiation and the mechanisms that lead to heavy chain diversification.