Arid3b Is Critical for B Lymphocyte Development

Jeffrey L. Kurkewich, Nathan Klopfenstein, William M. Hallas, Christian Wood, Rachel A. Sattler, Chhaya Das, Haley Tucker, Richard Dahl, Karen D.Cowden Dahl

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Arid3a and Arid3b belong to a subfamily of ARID (AT-rich interaction domain) transcription factors. The Arid family is involved in regulating chromatin accessibility, proliferation, and differentiation. Arid3a and Arid3b are closely related and share a unique REKLES domain that mediates their homo- And hetero-multimerization. Arid3a was originally isolated as a B cell transcription factor binding to the AT rich matrix attachment regions (MARS) of the immunoglobulin heavy chain intronic enhancer. Deletion of Arid3a results in a highly penetrant embryonic lethality with severe defects in erythropoiesis and hematopoietic stem cells (HSCs). The few surviving Arid3a-/- (<1%) animals have decreased HSCs and early progenitors in the bone marrow, but all mature lineages are normally represented in the bone marrow and periphery except for B cells. Arid3b-/- animals die around E7.5 precluding examination of hematopoietic development. So it is unclear whether the phenotype of Arid3a loss on hematopoiesis is dependent or independent of Arid3b. In this study we circumvented this limitation by also examining hematopoiesis in mice with a conditional allele of Arid3b. Bone marrow lacking Arid3b shows decreased common lymphoid progenitors (CLPs) and downstream B cell populations while the T cell and myeloid lineages are unchanged, reminiscent of the adult hematopoietic defect in Arid3a mice. Unlike Arid3a-/- mice, HSC populations are unperturbed in Arid3b-/- mice. This study demonstrates that HSC development is independent of Arid3b, whereas B cell development requires both Arid3a and Arid3b transcription factors.

Original languageEnglish (US)
Article numbere0161468
JournalPloS one
Volume11
Issue number8
DOIs
StatePublished - Aug 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Kurkewich, J. L., Klopfenstein, N., Hallas, W. M., Wood, C., Sattler, R. A., Das, C., Tucker, H., Dahl, R., & Dahl, K. D. C. (2016). Arid3b Is Critical for B Lymphocyte Development. PloS one, 11(8), [e0161468]. https://doi.org/10.1371/journal.pone.0161468