The development of early and mature B cells is impaired in mice deficient for the Ets-1 transcription factor.
The Ets-1 transcription factor is essential for normal development of the natural killer and T cell lineages; however, its role in B cell development remains poorly understood. To address this issue, we used gene targeting to inactivate Ets-1 in mice (Ets-1(-/-)). We show here that the development of B cell precursors, particularly steps requiring pre-B cell receptor function, is defective in Ets-1(-/-) mice. Peripheral B cell subsets were analyzed in RAG2-deficient mice reconstituted with Ets-1(-/-) fetal liver cells. In such Ets-1(-/-) chimeric mice, B cell precursors develop into IgM/IgD-bearing cells, but B-1a cells as well as transitional-2 and marginal zone B cell subsets of the spleen are absent. In response to B cell receptor stimulation, Ets-1(-/-) splenic B cells fail to express the CD69 and CD25 activation markers. Furthermore, despite activation of ERK and JNK signaling pathways, Ets-1-deficient B cells do not proliferate and die following BCR engagement. These findings demonstrate that the effect of Ets-1 inactivation is not restricted to the terminal B cell differentiation stage, but also affects the development and function of earlier B cell subsets.
Eyquem
Stéphanie
S
INSERM Unité 462, Paris, France.
Chemin
Karine
K
Fasseu
Magali
M
Chopin
Martine
M
Sigaux
François
F
Cumano
Ana
A
Bories
Jean-Christophe
JC
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D005434:Flow Cytometry; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010537:Peritoneum / Q000276:immunology; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D050783:Proto-Oncogene Proteins c-ets; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D011995:Recombination, Genetic / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology
D015703:Antigens, CD; C494042:Ets1 protein, mouse; D007143:Immunoglobulin Heavy Chains; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011947:Receptors, Antigen, B-Cell; D014157:Transcription Factors