As an approach to understanding development in the B lymphocyte lineage, Dr. Louis Staudt has characterized trans-acting factors that mediate lymphoid-specific gene transcription. As a model he has studied the lymphoid-specific transcription of immunoglobulin (Ig) genes. Oct-2 is a transcription factor expressed in B lymphocytes which is critical for the lymphoid-specific expression of immunoglobulin genes. Dr. Staudt's studies on Oct-2 in the past year have focused on his observation that Oct-2, in addition to being expressed in all B lymphocytes, is also expressed in some T lymphocytes, myeloid cells and in the fetal spinal cord. In T lymphocytes, Oct-2 is induced during activation of T lymphocytes by a variety of stimuli including cognate antigen. These findings suggest that Oct-2 controls gene expression in other cells besides B lymphocytes and must therefore cooperate with other B cell restricted transcription factors to fully account for lymphoid-specific gene expression. The molecular cloning of Oct-2 helped to identify a new class of transcription factors that share two structural domains, a homeobox and POUbox. Dr. Staudt has molecularly cloned and characterized a new member of this POU-homeobox family, termed Oct-3. Oct-3 binds to the same DNA motif as Oct-2, the octamer, but has a distinct pattern of expression. Oct-3 is expressed in the pluripotent stem cells of early mammalian embryos and is then down-modulated when these cells become committed to more differentiated lineages. Oct-3 expression is, however, maintained in cells of the germ line including primordial germ cells and oocytes. These findings place Oct-3 in marked contrast with previously studied homeobox genes which are not expressed in pluripotent stem cells or in the germ line but rather are expressed in cells that have differentiated along one of the somatic lineages. Oct-3, therefore, may be important for maintaining the pluripotent state and for committing a stem cell to the germ line lineage.
