The transcription factor GABP is a critical regulator of B lymphocyte development.
GA binding protein (GABP) is a ubiquitously expressed Ets-family transcription factor that critically regulates the expression of the interleukin-7 receptor alpha chain (IL-7Ralpha) in T cells, whereas it is dispensable for IL-7Ralpha expression in fetal liver B cells. Here we showed that deficiency of GABPalpha, the DNA-binding subunit of GABP, resulted in profoundly defective B cell development and a compromised humoral immune response, in addition to thymic developmental defects. Furthermore, the expression of Pax5 and Pax5 target genes such as Cd79a was greatly diminished in GABPalpha-deficient B cell progenitors, pro-B, and mature B cells. GABP could bind to the regulatory regions of Pax5 and Cd79a in vivo. Thus, GABP is a key regulator of B cell development, maturation, and function.
Xue
Hai-Hui
HH
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674, USA.
Bollenbacher-Reilley
Julie
J
Wu
Zheng
Z
Spolski
Rosanne
R
Jing
Xuefang
X
Zhang
Yi-Chen
YC
McCoy
J Philip
JP
Leonard
Warren J
WJ
D020121:5' Untranslated Regions / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D051925:CD79 Antigens / Q000235:genetics; D002478:Cells, Cultured; D051268:GA-Binding Protein Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008817:Mice, Mutant Strains; D051757:PAX5 Transcription Factor / Q000235:genetics; D011401:Promoter Regions, Genetic; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D020121:5' Untranslated Regions; D051925:CD79 Antigens; D051268:GA-Binding Protein Transcription Factor; C495656:Gabpa protein, mouse; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse