Ikaros is critical for B cell differentiation and function

• Published in: European journal of immunology 2002-03, Vol.32 (3), p.720-730
• Main Authors: Kirstetter, Peggy, Thomas, Mireille, Dierich, Andrée, Kastner, Philippe, Chan, Susan
• Format: Article
• Language: English
• Subjects: Animals; Antibody Formation; Antigens, Differentiation, B-Lymphocyte - biosynthesis; Antigens, Differentiation, B-Lymphocyte - genetics; B cell; B-Lymphocytes - cytology; B-Lymphocytes - immunology; beta-Galactosidase - genetics; Bone Marrow Cells - immunology; Cell Differentiation; Cell Lineage; Differentiation; 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; Ikaros protein; Ikaros Transcription Factor; Immunoglobulin Isotypes - biosynthesis; Immunoglobulin M - biosynthesis; Immunologic Deficiency Syndromes - embryology; Immunologic Deficiency Syndromes - etiology; Immunologic Deficiency Syndromes - genetics; Immunology; Knockout; Lac Operon; Life Sciences; Mice; Mice, Transgenic; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors - genetics; Transcription Factors - physiology; Transcription, Genetic
• ISSN: 0014-2980; 1521-4141
• 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 β‐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 λ5. These abnormalities suggest a partial block atthe 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.