Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus.
Open Access
- 15 February 1997
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 11 (4), 476-491
- https://doi.org/10.1101/gad.11.4.476
Abstract
The Pax5 gene coding for the transcription factor BSAP has an essential role in B lymphopoiesis and midbrain development. Here we present a detailed analysis of the B-cell phenotype of Pax5 mutant mice that revealed a differential dependency of fetal and adult B lymphopoiesis on this transcriptional regulator. B-cell development is arrested in the bone marrow at the early pro-B (pre-BI) cell stage, which is characterized by expression of the early markers c-kit, CD43, lambda5, VpreB, and HSA and the absence of the later markers CD25 and BP-1. These pre-BI cells fail to express the BSAP target gene CD19 and are capable of long-term proliferation in vitro in the presence of stromal cells and IL-7. B-lymphoid progenitors could not be detected in the fetal liver of Pax5 mutant embryos. However, Pax5-deficient fetal liver cells gave rise to the development of pre-BI cells in bone marrow on transplantation into lethally irradiated mice. These data indicate different functions of Pax5 in the distinctive microenvironments of fetal liver and adult bone marrow. As shown by PCR analyses, the pre-BI cells in Pax5-deficient bone marrow have undergone D(H)-to-J(H) rearrangement of the immunoglobulin heavy-chain locus at normal frequency. In contrast, V(H)-to-D(H)J(H) rearrangements were reduced approximately 50-fold in Pax5-deficient pre-BI cells, suggesting a role for Pax5 in the developmental pathway controlling V-to-DJ recombination.Keywords
This publication has 81 references indexed in Scilit:
- Self‐renewal of B‐1 lymphocytes is dependent on CD19European Journal of Immunology, 1996
- Requirement of Transcription Factor PU.1 in the Development of Multiple Hematopoietic LineagesScience, 1994
- Analysis of the B-cell progenitor compartment at the level of single cellsCurrent Biology, 1994
- Regulation of gene expression at early stages of B-cell differentiationCurrent Opinion in Immunology, 1994
- Immunoglobulin heavy and light chain genes rearrange independently at early stages of B cell developmentCell, 1993
- Helix-loop-helix transcription factor E47 activates germ-line immunoglobulin heavy-chain gene transcription and rearrangement in a pre-T-cell line.Genes & Development, 1991
- B cell development regulated by gene rearrangement: Arrest of maturation by membrane-bound Dμ protein and selection of DH element reading framesCell, 1991
- Virus-transformed pre-B cells show ordered activation but not inactivation of immunoglobulin gene rearrangement and transcription.The Journal of Experimental Medicine, 1991
- RAG-1 and RAG-2, Adjacent Genes That Synergistically Activate V(D)J RecombinationScience, 1990
- Developmental regulation of micro-injected histone genes in sea urchin embryosDevelopmental Biology, 1988