Lymphocytes are derived from hematopoietic stem cells (HSC) following a ser
ies of regulated differentiation events. Multipotent HSCs become committed
to the B cell lineage in bone marrow and the T cell lineage in the thymus a
fter receiving appropriate signals from the corresponding microenvironment.
These committed lymphoid cells must then undergo V(D)J recombination at th
e immunoglobulin gene or T cell receptor gene locus resulting in clonal pro
duction of functional B or T lymphocytes, respectively. Lymphocyte commitme
nt and differentiation are accompanied by programmed gene expression or rep
ression events which are driven by lineage and stage specific transcription
factors. The basic-helix-io op-helix (bHLH) transcription factors encoded
by the E2A gene are involved in several differentiation events during B and
T cell development, including lineage commitment, initiation of V(D)J reco
mbination, and antigen receptor mediated proliferation and differentiation.
Several recent reviews have provided a comprehensive discussion of biochem
ical, cellular, and genetic research on E2A function in lymphocyte developm
ent (1,2). Here, we only discuss some of the genetic approaches our laborat
ory (except where it is noted) has undertaken to investigate the molecular
pathways mediated by E2A transcription factors in lymphocyte development.