This grant has supported studies on various aspects of class switching and lymphokine induction in the spontaneous murine B leukemia, BCL1. Our findings during the last period have prompted a broader investigation of B cell differentiation using this model system and normal B cells. Based on significant supporting data, we have condensed our continuing efforts into three projects. First, we want to determine the precise mechanism and its control for allelically excluded, dual synthesis of mu and gamma1 chains in BCL1 subclones. We know that this occurs by some form of discontinuous transcription, and not by production of a 'long transcript' covering the entire VDJ to C-gamma1 region. Second, we want to determine precisely how IL-5 and IL-6 in conjunction with antigen induce increased rates of u transcription and DNA replication in BCL1 cells rendered antigen-specific by transfection. We have identified the target sequences and the protein-DNA interactions for IL-5+Ag. We want to do the same with IL-6 plus go after the factors induced by both lymphokines. Third, we want to study proteins expressed only at the immature/mature B cell differentiation stage based on the premise that functions relevant to Ig gene expression will be discovered. We have cloned from BCL1 two mRNAs that satisfy the criteria of cell type- and stage-specificity.
Showing the most recent 10 out of 54 publications
