Regulation of VH replacement by B cell receptor-mediated signaling in human immature B cells

Jing Liu, Miles D. Lange, Sang Yong Hong, Wanqin Xie, Kerui Xu, Lin Huang, Yangsheng Yu, Götz R A Ehrhardt, Michael Zemlin, Peter D. Burrows, Kaihong Su, Robert H. Carter, Zhixin Zhang

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

VH replacement provides a unique RAG-mediated recombination mechanism to edit nonfunctional IgH genes or IgH genes encoding self-reactive BCRs and contributes to the diversification of Ab repertoire in the mouse and human. Currently, it is not clear how VH replacement is regulated during early B lineage cell development. In this article, we show that cross-linking BCRs induces VH replacement in human EU12 μHC + cells and in the newly emigrated immature B cells purified from peripheral blood of healthy donors or tonsillar samples. BCR signaling-induced VH replacement is dependent on the activation of Syk and Src kinases but is inhibited by CD19 costimulation, presumably through activation of the PI3K pathway. These results show that VH replacement is regulated by BCR-mediated signaling in human immature B cells, which can be modulated by physiological and pharmacological treatments.

Original languageEnglish (US)
Pages (from-to)5559-5566
Number of pages8
JournalJournal of Immunology
Volume190
Issue number11
DOIs
StatePublished - Jun 1 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Liu, J., Lange, M. D., Hong, S. Y., Xie, W., Xu, K., Huang, L., Yu, Y., Ehrhardt, G. R. A., Zemlin, M., Burrows, P. D., Su, K., Carter, R. H., & Zhang, Z. (2013). Regulation of VH replacement by B cell receptor-mediated signaling in human immature B cells. Journal of Immunology, 190(11), 5559-5566. https://doi.org/10.4049/jimmunol.1102503