Ikaros is critical for B cell differentiation and function

Eur J Immunol. 2002 Mar;32(3):720-30. doi: 10.1002/1521-4141(200203)32:3<720::AID-IMMU720>3.0.CO;2-P.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation
  • Antigens, Differentiation, B-Lymphocyte / biosynthesis
  • Antigens, Differentiation, B-Lymphocyte / genetics
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Bone Marrow Cells / immunology
  • Cell Differentiation
  • Cell Lineage
  • DNA Nucleotidylexotransferase / biosynthesis
  • DNA Nucleotidylexotransferase / genetics
  • DNA-Binding Proteins
  • Fetus / immunology
  • Gene Expression Regulation, Developmental
  • Gene Targeting
  • Genes, RAG-1
  • Genes, Reporter
  • Genotype
  • Homeodomain Proteins / biosynthesis
  • Ikaros Transcription Factor
  • Immunoglobulin Isotypes / biosynthesis
  • Immunoglobulin M / biosynthesis
  • Immunologic Deficiency Syndromes / embryology
  • Immunologic Deficiency Syndromes / etiology
  • Immunologic Deficiency Syndromes / genetics
  • Lac Operon
  • Mice
  • Mice, Transgenic
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • beta-Galactosidase / genetics


  • Antigens, Differentiation, B-Lymphocyte
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Immunoglobulin Isotypes
  • Immunoglobulin M
  • Rag2 protein, mouse
  • Transcription Factors
  • V(D)J recombination activating protein 2
  • Zfpn1a1 protein, mouse
  • RAG-1 protein
  • Ikaros Transcription Factor
  • DNA Nucleotidylexotransferase
  • beta-Galactosidase