Early growth response genes regulate B cell development, proliferation, and immune response.
Egr-1 (early growth response gene-1) is an immediate early gene encoding a zinc finger motif-containing transcription factor. Upon cross-linking of BCR, mature B cells undergo proliferation with an increase in Egr-1 message. Immature B lymphoma cells that express Egr-1 message and protein constitutively are growth inhibited when Egr-1 is down-regulated by negative signals from BCR or by antisense oligonucleotides. To test the hypothesis that Egr-1 is important for B cell development, we examined B cells from primary and secondary lymphoid organs in Egr-1(-/-) mice. Marginal zone B cell development was arrested in these mice, whereas the B cells in all other compartments were increased. To test the hypothesis that Egr-1 function may be partially compensated by other Egr family members, we developed transgenic mice expressing a dominant negative form of Egr-1, which lacks the trans activation domain but retains the DNA-binding domain, in a B cell-specific manner. There was a decrease in B lymphopoiesis in the bone marrow accompanied by a reduction in splenic immature and mature B cells as well as marginal zone B cells in the transgenic mice. Moreover, transgenic mice respond poorly to BCR cross-linking in vitro and T-independent and T-dependent Ags in vivo.
Gururajan
Murali
M
Departments of Microbiology, University of Kentucky, Lexington, KY 40536, USA.
Simmons
Alan
A
Dasu
Trivikram
T
Spear
Brett T
BT
Calulot
Christopher
C
Robertson
Darrell A
DA
Wiest
David L
DL
Monroe
John G
JG
Bondada
Subbarao
S
D000818:Animals; D000955:Antigens, T-Independent / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051766:Early Growth Response Protein 1 / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D005260:Female; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000502:physiology
D000955:Antigens, T-Independent; D051766:Early Growth Response Protein 1; D011947:Receptors, Antigen, B-Cell
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