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

Academic Article

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.
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    Keywords

  • Antigens, CD19, Base Sequence, Cell Differentiation, Cell Line, Enzyme Activation, Gene Rearrangement, Humans, Immunoglobulin Heavy Chains, Immunoglobulin Variable Region, Intracellular Signaling Peptides and Proteins, Molecular Sequence Data, Palatine Tonsil, Precursor Cells, B-Lymphoid, Protein-Tyrosine Kinases, Receptors, Antigen, B-Cell, Signal Transduction, Syk Kinase, src-Family Kinases
  • Digital Object Identifier (doi)

    Authorlist

  • Liu J; Lange MD; Hong SY; Xie W; Xu K; Huang L; Yu Y; Ehrhardt GRA; Zemlin M; Burrows PD
  • Start Page

  • 5559
  • End Page

  • 5566
  • Volume

  • 190
  • Issue

  • 11