GABPbeta2 is dispensible for normal lymphocyte development but moderately affects B cell responses.
GA-binding protein (GABP) is the only Ets family transcription factor that functions as a heterodimer. The GABPalpha subunit binds to DNA, and the GABPbeta subunit possesses the ability to transactivate target genes. Inactivation of GABPalpha caused embryonic lethality and defective lymphocyte development and immune responses. There are 3 isoforms of the GABPbeta subunit, but whether they have distinct functions has not been addressed. In this study, we selectively ablated the expression of GABPbeta2 using a gene trap strategy. GABPbeta2-deficient mice were viable and had normal T and B cell development, suggesting that loss of GABPbeta2 is compensated for by other GABPbeta isoforms during these processes. GABPbeta2-deficient T cells can be activated and proliferate similarly to wild-type controls. In contrast, B cells lacking GABPbeta2 showed 2-3-fold increases in proliferation in response to B cell receptor stimulation. In addition, GABPbeta2-deficient mice exhibited moderately increased antibody production and germinal center responses when challenged with T-dependent antigens. These results indicate that albeit GABPbeta isoforms are redundant in lymphocyte development, GABPbeta2 has a distinct role in restraining B cell expansion and humoral responses.
Jing
Xuefang
X
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Zhao
Dong-Mei
DM
Waldschmidt
Thomas J
TJ
Xue
Hai-Hui
HH
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D020964:Embryo Loss / Q000235:genetics / Q000276:immunology; D051268:GA-Binding Protein Transcription Factor / Q000235:genetics / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000819:agonists / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D015533:Transcriptional Activation / Q000235:genetics / Q000276:immunology
D000941:Antigens; D051268:GA-Binding Protein Transcription Factor; C495659:Gabpb2 protein, mouse; D020033:Protein Isoforms; D011947:Receptors, Antigen, B-Cell