The transcription factor early growth response 1 (Egr-1) advances differentiation of pre-B and immature B cells

被引:54
作者
Dinkel, A
Warnatz, K
Ledermann, B
Rolink, A
Zipfel, PF
Bürki, K
Eibel, H
机构
[1] Univ Hosp, Clin Res Unit Rheumatol, Div Clin Immunol & Rheumatol, D-79106 Freiburg, Germany
[2] Novartis Ltd, Preclin Res, CH-4058 Basel, Switzerland
[3] Basel Inst Immunol, CH-4058 Basel, Switzerland
[4] Bernhard Nocht Inst Trop Med, D-20359 Hamburg, Germany
关键词
Egr-1; transcription factor; B cell development; BP-1; nur77;
D O I
10.1084/jem.188.12.2215
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 transcript in pro/pre-B and immature B lymphocytes,. and Egr-1 protein in pro/pre-B-I cells cultivated on stroma cells ill 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 front the B220(low) BP-1(-) IL-2R(-) pro/prw-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.
引用
收藏
页码:2215 / 2224
页数:10
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