Immunoglobulin molecules (Ig) consist of heavy and light chains and are expressed in B-cells to diversity of antigens. Igs acquire their antigen recognition properties in a process of DNA deletion called VDJ recombination. Unsuccessful expression of the recombined Ig leads to failure of B-cell maturation, numerous infections and premature death of the affected individual. Abelson cell lines have the phenotype of a pre-B- cell and have been used to study how Ig expression affects B-cell maturation. The accessibility hypothesis proposes that regulated Ig expression in B-cells is governed in part by the transcriptional and VDJ recombinase activities to target the Ig locus. Recent experiments suggest that selective chromatin reorganization of the Ig locus may play a role in controlling accessibility to transcriptional and recombinase activities in B- cell-specific manner. The experiments proposed in this fellowship exploit inducible light chain (kappa) gene reorganization in Abelson cell lines to develop a highly purified in vitro system that faithfully mimics VDJ recombination signaled Ig locus remodeling. This system will investigate a proposed activity endogenously present in Abelson cells that either specifically recognizes and directly remodels or specifically recognizes and recruits a """"""""general remodeling machinery"""""""" to the kappa locus for chromatin reorganization upon induction of VDJ rearrangement.
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