LncRNA00492 is required for marginal zone B-cell development

Immunology. 2022 Jan;165(1):88-98. doi: 10.1111/imm.13408. Epub 2021 Sep 7.

Abstract

B-cell development undergoes a series of steps from the bone marrow to the secondary lymphoid organs. A defect in B-cell development can lead to immunodeficiency or malignant disorders, such as leukaemia or lymphoma. Long non-coding RNAs have been reported to act as important regulators of many pathological processes. However, very little is known regarding the role of lncRNAs during B-cell development and the regulation of their expression. In this study, we explored the expression and role of lncRNA Gme00492 in B-cell development. We observed that lnc00492 was highly expressed in B-cell development and primarily expressed in the nucleus. Lnc00492-deficient mice had fewer marginal zone B cells in the spleen, likely due to a developmental block. Importantly, lnc00492 interacts with CTBP1 and targets it for ubiquitination and degradation during B-cell development, whereas the transcriptional corepressor factor CTBP1 plays a critical role in Notch2 signalling. Thus, we identified a novel regulatory axis between lnc00492 and CTBP1 in B cells, suggesting that lnc00492 is essential for marginal zone B-cell development.

Keywords: B-cell development; CTBP1; Lnc00492; marginal zone B cells; notch2 signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / metabolism
  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Biomarkers
  • Bone Marrow / immunology
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Cell Differentiation / genetics*
  • Cell Differentiation / immunology
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Immunophenotyping
  • Lymphopoiesis / genetics*
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Protein Binding
  • RNA, Long Noncoding / genetics*
  • Receptor, Notch2 / metabolism
  • Signal Transduction
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • Ubiquitination

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • RNA, Long Noncoding
  • Receptor, Notch2
  • Alcohol Oxidoreductases
  • C-terminal binding protein