G. Bain et al., E2A PROTEINS ARE REQUIRED FOR PROPER B-CELL DEVELOPMENT AND INITIATION OF IMMUNOGLOBULIN GENE REARRANGEMENTS, Cell, 79(5), 1994, pp. 885-892
E12 and E47 are two helix-loop-helix transcription factors that arise
by alternative splicing of the E2A gene. Both have been implicated in
the regulation of immunoglobulin gene expression. We have now generate
d E2A (-/-) mice by gene targeting. E2A-null mutant mice fail to gener
ate mature B cells. The arrest of B cell development occurs at an earl
y stage, since no immunoglobulin DJ rearrangements can be detected in
homozygous mutant mice. While immunoglobulin germline I-mu RAG-1, mb-1
, CD19, and lambda 5 transcripts are dramatically reduced in fetal liv
ers of E2A (-/-) mice, B29 and mu degrees transcripts are present, but
at lower levels. In addition, we show that Pax-5 transcripts are sign
ificantly reduced in fetal livers of E2A (-/-) mice. These data sugges
t a crucial role for E2A products as central regulators in early B cel
l differentiation.