The transcription factor Fli-1 modulates marginal zone and follicular B cell development in mice.
Fli-1 belongs to the Ets transcription factor family and is expressed primarily in hematopoietic cells, including most cells active in immunity. To assess the role of Fli-1 in lymphocyte development in vivo, we generated mice that express a truncated Fli-1 protein, lacking the C-terminal transcriptional activation domain (Fli-1(DeltaCTA)). Fli-1(DeltaCTA)/Fli-1(DeltaCTA) mice had significantly fewer splenic follicular B cells, and an increased number of transitional and marginal zone B cells, compared with wild-type controls. Bone marrow reconstitution studies demonstrated that this phenotype is the result of lymphocyte intrinsic effects. Expression of Igalpha and other genes implicated in B cell development, including Pax-5, E2A, and Egr-1, are reduced, while Id1 and Id2 are increased in Fli-1(DeltaCTA)/Fli-1(DeltaCTA) mice. Proliferation of B cells from Fli-1(DeltaCTA)/Fli-1(DeltaCTA) mice was diminished, although intracellular Ca(2+) flux in B cells from Fli-1(DeltaCTA)/Fli-1(DeltaCTA) mice was similar to that of wild-type controls after anti-IgM stimulation. Immune responses and in vitro class switch recombination were also altered in Fli-1(DeltaCTA)/Fli-1(DeltaCTA) mice. Thus, Fli-1 modulates B cell development both centrally and peripherally, resulting in a significant impact on the in vivo immune response.
Zhang
Xian K
XK
Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA. zhangjo@musc.edu
Moussa
Omar
O
LaRue
Amanda
A
Bradshaw
Sarah
S
Molano
Ivan
I
Spyropoulos
Demetri D
DD
Gilkeson
Gary S
GS
Watson
Dennis K
DK
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051789:Proto-Oncogene Protein c-fli-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
C497426:Fli1 protein, mouse; D007074:Immunoglobulin G; D051789:Proto-Oncogene Protein c-fli-1; D011947:Receptors, Antigen, B-Cell