1. The Transcription Factor GABP Is a Critical Regulator of B Lymphocyte Development
- Author
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Xuefang Jing, Yi-Chen Zhang, J. Philip McCoy, Warren J. Leonard, Hai-Hui Xue, Zheng Wu, Julie Bollenbacher-Reilley, and Rosanne Spolski
- Subjects
T-Lymphocytes ,Lymphocyte ,Immunology ,Regulator ,Gene Expression ,Bone Marrow Cells ,Biology ,Mice ,Immune system ,medicine ,Animals ,Immunology and Allergy ,Progenitor cell ,Promoter Regions, Genetic ,Receptor ,MOLIMMUNO ,Transcription factor ,Cells, Cultured ,B cell ,B-Lymphocytes ,PAX5 Transcription Factor ,Gene Expression Regulation, Developmental ,GA-Binding Protein Transcription Factor ,Molecular biology ,Mice, Mutant Strains ,Infectious Diseases ,medicine.anatomical_structure ,Regulatory sequence ,5' Untranslated Regions ,CD79 Antigens ,Spleen - Abstract
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.
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