Rapid Identification of Novel Human Lymphoid-Restricted Genes by Automated DNA Sequencing of Subtracted cDNA Libraries

Abstract

The long term interest of our laboratory has been in identifying nuclear regulatory factors that control the differentiation and function of B lymphocytes. This interest began with the identification of a lymphoid-restricted transcription factor, Oct-2, which binds to the highly conserved octamer motif in the promoter regions of immunoglobulin genes (1,2). Through the work of many laboratories, this factor was cloned and found to contain a DNA binding domain belonging to the homeodomain family (3–7). In view of the profound importance of homeodomain proteins in many developing systems, it was initially hoped that Oct-2 would be required for the development of the B lymphoid lineage. Subsequent analysis has suggested, however, that Oct-2 must act in concert with other transcription factors to fully direct B cell development. Firstly, Oct-2 is not confined in expression to B lymphocytes: it is readily detected in the central nervous system (8) and in T lymphocytes (9) and thus may play a role in these lineages. Most telling was the inactivation of Oct-2 by homologous recombination in the mouse (10). These Oct-2 “knock-out” mice died shortly after birth for unknown reasons but at the time of death, B cell development appeared relatively normal. The B lymphocytes did, however, have a functional deficit in their response to bacterial lipopolysaccharide. Thus, Oct-2 appears to be dispensable for much of B cell development but it does control an aspect of mature B cell function.