Y Chromosome–Linked B and NK Cell Deficiency in Mice
Open Access
- 15 June 2013
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 190 (12), 6209-6220
- https://doi.org/10.4049/jimmunol.1300303
Abstract
There are no primary immunodeficiency diseases linked to the Y chromosome, because the Y chromosome does not contain any vital genes. We have established a novel mouse strain in which all males lack B and NK cells and have Peyer’s patch defects. By 10 wk of age, 100% of the males had evident immunodeficiencies. Mating these immunodeficient males with wild-type females on two different genetic backgrounds for several generations demonstrated that the immunodeficiency is linked to the Y chromosome and is inherited in a Mendelian fashion. Although multicolor fluorescence in situ hybridization analysis showed that the Y chromosome in the mutant male mice was one third shorter than that in wild-type males, exome sequencing did not identify any significant gene mutations. The precise molecular mechanisms are still unknown. Bone marrow chimeric analyses demonstrated that an intrinsic abnormality in bone marrow hematopoietic cells causes the B and NK cell defects. Interestingly, fetal liver cells transplanted from the mutant male mice reconstituted B and NK cells in lymphocyte-deficient Il2rg−/− recipient mice, whereas adult bone marrow transplants did not. Transducing the EBF gene, a master transcription factor for B cell development, into mutant hematopoietic progenitor cells rescued B cell but not NK cell development both in vitro and in vivo. These Y chromosome–linked immunodeficient mice, which have preferential B and NK cell defects, may be a useful model of lymphocyte development.Keywords
This publication has 33 references indexed in Scilit:
- NK cell development, homeostasis and function: parallels with CD8+ T cellsNature Reviews Immunology, 2011
- STAT5 in B cell development and leukemiaCurrent Opinion in Immunology, 2010
- Primary B Cell Immunodeficiencies: Comparisons and ContrastsAnnual Review of Immunology, 2009
- Co‐inhibitory roles for glucocorticoid‐induced TNF receptor in CD1d‐dependent natural killer T cellsEuropean Journal of Immunology, 2008
- Mature natural killer cell and lymphoid tissue–inducing cell development requires Id2-mediated suppression of E protein activityThe Journal of Experimental Medicine, 2007
- Developmental switch of mouse hematopoietic stem cells from fetal to adult type occurs in bone marrow after birthProceedings of the National Academy of Sciences of the United States of America, 2006
- Autoreactive B Cell Responses to RNA-Related Antigens Due to TLR7 Gene DuplicationScience, 2006
- Complementary Signaling through flt3 and Interleukin-7 Receptor α Is Indispensable for Fetal and Adult B Cell GenesisThe Journal of Experimental Medicine, 2003
- Abnormal Development of Intestinal Intraepithelial Lymphocytes and Peripheral Natural Killer Cells in Mice Lacking the IL-2 Receptor β ChainThe Journal of Experimental Medicine, 1997
- Molecular Approaches to Analysis of X-Linked ImmunodeficienciesAnnual Review of Immunology, 1992