The endoplasmic reticulum–resident E3 ubiquitin ligase Hrd1 controls a critical checkpoint in B cell development in mice

Yi Yang, Sinyi Kong, Yana Zhang, Johanna Melo-Cardenas, Beixue Gao, Yusi Zhang, Donna D. Zhang, Bin Zhang, Jianxun Song, Edward Thorp, Kezhong Zhang, Jinping Zhang, Deyu Fang

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Humoral immunity involves multiple checkpoints that occur in B cell development, maturation, and activation. The pre–B-cell receptor (pre-BCR) is expressed following the productive recombination of the immunoglobulin heavy-chain gene, and sSignalsing through the pre-BCR are required for the differentiation of pre–B cells into immature B cells. However, the molecular mechanisms controlling the pre-BCR expression and signaling strength remain undefined. Herein, we probed the role of the endoplasmic reticulum–associated, stress-activated E3 ubiquitin ligase HMG-CoA reductase degradation 1 (Hrd1) in B cell differentiation. Using mice with a specific Hrd1 deletion in pro–B cells and subsequent B cell developmental stages, we showed that the E3 ubiquitin ligase Hrd1 governs a critical checkpoint during B cell development. We observed that Hrd1 is required for degradation of the pre-BCR complex during the early stage of B cell development. As a consequence, loss of Hrd1 in the B cell lineage resulted in increased pre-BCR expression levels and a developmental defect in the transition from large to small pre–B cells. This defect, in turn, resulted in reduced fewer mature B cells in bone marrow and peripheral lymphoid organs.

Original languageEnglish (US)
Pages (from-to)12934-12944
Number of pages11
JournalJournal of Biological Chemistry
Volume293
Issue number33
StatePublished - Aug 17 2018

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yang, Y., Kong, S., Zhang, Y., Melo-Cardenas, J., Gao, B., Zhang, Y., Zhang, D. D., Zhang, B., Song, J., Thorp, E., Zhang, K., Zhang, J., & Fang, D. (2018). The endoplasmic reticulum–resident E3 ubiquitin ligase Hrd1 controls a critical checkpoint in B cell development in mice. Journal of Biological Chemistry, 293(33), 12934-12944.