Ikaros is critical for B cell differentiation and function.
The Ikaros gene encodes a zinc-finger transcription factor required during early B cell development, as B-lineage cells are absent in mice lacking Ikaros. Here we describe a novel Ikaros-targeted mouse line carrying a beta-galactosidase reporter in which low amounts of Ikaros proteins remain expressed. In homozygote animals, B cells are absent during fetal development, but develop postnatally from a reduced pool of precursors. In vitro, the proliferation and differentiation of B-lineage progenitors are severely impaired. These defects are attenuated in vivo, but bone marrow B cells display an unusual pattern of cell surface marker expression and show decreased transcript levels for TdT, Rag-1, Rag-2 and lambda 5. These abnormalities suggest a partial block at the proB cell stage of differentiation. In the periphery, mature B cells exhibit a lower activation threshold but form fewer germinal centers in response to antigenic stimulation. Our results show that Ikaros controls multiple aspects of B cell differentiation and function.
Kirstetter
Peggy
P
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS-INSERM-ULP, Illkirch, France.
Thomas
Mireille
M
Dierich
Andrée
A
Kastner
Philippe
P
Chan
Susan
S
D000818:Animals; D000917:Antibody Formation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage; D004253:DNA Nucleotidylexotransferase / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins; D005333:Fetus / Q000276:immunology; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D016654:Genes, RAG-1; D017930:Genes, Reporter; D005838:Genotype; D018398:Homeodomain Proteins / Q000096:biosynthesis; D051740:Ikaros Transcription Factor; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007153:Immunologic Deficiency Syndromes / Q000196:embryology / Q000209:etiology / Q000235:genetics; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000235:genetics
D000944:Antigens, Differentiation, B-Lymphocyte; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; C499308:Rag2 protein, mouse; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2; C497238:Zfpn1a1 protein, mouse; C064658:RAG-1 protein; D051740:Ikaros Transcription Factor; D004253:DNA Nucleotidylexotransferase; D001616:beta-Galactosidase