Genetic analysis of transcription factors implicated in B lymphocyte development.

The transcription factors Oct-2, NF-kappa B and PU.1 have been implicated in regulating the development of B lymphocytes. Genetic approaches have been used to analyze the developmental functions of these regulatory proteins. Using gene targeting in murine embryonic stem cells, PU.1 is shown to be required for the development of progenitor B cells. Strikingly, PU.1 is also essential for the development of T lymphoid, granulocytic and monocytic progenitors. Transcription factors of the NF-kappa B/Rel family, which appear to regulate immunoglobulin kappa gene expression, are shown to be a target of the viral transforming protein (v-abl) which arrests B lineage development at the precursor B stage. This suggests a mechanism by which v-abl blocks precursor B cell differentiation. The Oct-2 transcription factor was considered to represent a development regulator of immunoglobulin gene expression. Using gene targeting in a murine B cell, Oct-2 is shown to be dispensable for immunoglobulin gene expression. This suggests the existence of an alternate pathway, involving the ubiquitous related protein, Oct-1, in immunoglobulin gene regulation.