PUBLICATION

Loss of runx1 function results in B cell immunodeficiency but not T cell in adult zebrafish.

Authors
Chi, Y., Huang, Z., Chen, Q., Xiong, X., Chen, K., Xu, J., Zhang, Y., Zhang, W.
ID
ZDB-PUB-180727-5
Date
2018
Source
Open Biology   8(7): (Journal)
Registered Authors
Chi, Yali, Huang, Zhibin, Xiong, Xiaojie, Zhang, Wenqing, Zhang, Yiyue
Keywords
Runx1 mutation, immunodeficiency, lymphocyte, zebrafish
MeSH Terms
  • Animals
  • Apoptosis
  • B-Lymphocytes/cytology
  • B-Lymphocytes/immunology*
  • Core Binding Factor Alpha 2 Subunit/deficiency
  • Core Binding Factor Alpha 2 Subunit/genetics*
  • Evolution, Molecular
  • Immunoglobulins/genetics
  • Immunoglobulins/metabolism
  • Mutation
  • T-Lymphocytes/cytology
  • T-Lymphocytes/immunology*
  • V(D)J Recombination
  • Zebrafish/genetics*
  • Zebrafish/immunology
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics*
PubMed
30045885 Full text @ Open Biol.
Abstract
Transcription factor RUNX1 holds an integral role in multiple-lineage haematopoiesis and is implicated as a cofactor in V(D)J rearrangements during lymphocyte development. Runx1 deficiencies resulted in immaturity and reduction of lymphocytes in mice. In this study, we found that runx1W84X/W84X mutation led to the reduction and disordering of B cells, as well as the failure of V(D)J rearrangements in B cells but not T cells, resulting in antibody-inadequate-mediated immunodeficiency in adult zebrafish. By contrast, T cell development was not affected. The decreased number of B cells mainly results from excessive apoptosis in immature B cells. Disrupted B cell development results in runx1W84X/W84X mutants displaying a similar phenotype to common variable immunodeficiency-a primary immunodeficiency disease primarily characterized by frequent susceptibility to infection and deficient immune response, with marked reduction of antibody production of IgG, IgA and/or IgM. Our studies demonstrated an evolutionarily conserved function of runx1 in maturation and differentiation of B cells in adult zebrafish, which will serve as a valuable model for the study of immune deficiency diseases and their treatments.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping