The transcription factor early growth response 1 (Egr-1) advances differentiation of pre-B and immature B cells.
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.
Dinkel
A
A
Clinical Research Unit for Rheumatology, Division of Rheumatology and Clinical Immunology, University Hospital Freiburg, D-79106 Freiburg, Germany.
Warnatz
K
K
Ledermann
B
B
Rolink
A
A
Zipfel
P F
PF
Bürki
K
K
Eibel
H
H
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051766:Early Growth Response Protein 1; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D017874:Immediate-Early Proteins; D019891:Leukopoiesis; D008099:Liver / Q000196:embryology; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009154:Mutation; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D020218:Response Elements / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; C499308:Rag2 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2; D004247:DNA; C062906:BP-1-6C3 antigen; D008666:Metalloendopeptidases