The transcription factor early growth response 1 (Egr-1) advances differentiation of pre-B and immature B cells.
J Exp Med
; 188(12): 2215-24, 1998 Dec 21.
Article
em En
| MEDLINE
| ID: mdl-9858508
ABSTRACT
In mature B lymphocytes, the zinc finger transcription factor early growth response 1 (Egr-1) is one of the many immediate-early genes induced upon B cell antigen receptor engagement. However, its role during earlier stages of lymphopoiesis has remained unclear. By examining bone marrow B cell subsets, we found Egr-1 transcripts in pro/pre-B and immature B lymphocytes, and Egr-1 protein in pro/pre-B-I cells cultivated on stroma cells in the presence of interleukin (IL)-7. In recombinase-activating gene (RAG)-2-deficient mice overexpressing an Egr-1 transgene in the B lymphocyte lineage, pro/pre-B-I cells could differentiate past a developmental block at the B220(low) BP-1(-) stage to the stage of B220(low) BP-1(+) pre-B-I cells, but not further to the B220(low) BP-1(+) CD25(+) stage of pre-B-II cells. Therefore, during early B lymphopoiesis progression from the B220(low) BP-1(-) IL-2R- pro/pre-B-I stage to the B220(low) BP-1(+) IL-2R+ pre-B-II stage seems to occur in at least two distinct steps, and the first step to the stage of B220(low) BP-1(+) pre-B-I cells can be promoted by the overexpression of Egr-1 alone. Wild-type mice expressing an Egr-1 transgene had increased proportions of mature immunoglobulin (Ig)M+ B220(high) and decreased proportions of immature IgM+ B220(low) bone marrow B cells. Since transgenic and control precursor B cells show comparable proliferation patterns, overexpression of Egr-1 seems also to promote entry into the mature B cell stage. Analysis of changes in the expression pattern of potential Egr-1 target genes revealed that Egr-1 enhances the expression of the aminopeptidase BP-1/6C3 in pre-B and immature B cells and upregulates expression of the orphan nuclear receptor nur77 in IgM+ B cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Células-Tronco Hematopoéticas
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Linfócitos B
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Proteínas Imediatamente Precoces
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Leucopoese
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Proteínas de Ligação a DNA
Limite:
Animals
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Alemanha