Syk is indispensable for CpG-induced activation and differentiation of human B cells

Mariann Kremlitzka, Bernadett Mácsik-Valent, Anna Erdei

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

B cells are efficiently activated by CpG oligodeoxynucleotides (ODNs) to produce pro-inflammatory cytokines and antibody (Ab). Here, we describe a so far unidentified, spleen tyrosine kinase (Syk)-dependent pathway, which is indispensable for CpG-induced human B cell activation. We show that triggering of B cells by CpG results in Syk and src kinase phosphorylation, proliferation, as well as cytokine and Ab production independent of the BCR. Notably, all these functions are abrogated when Syk is inhibited. We demonstrate that CpG-induced Syk activation originates from the cell surface in a TLR9-dependent manner. While inhibition of Syk does not influence the uptake of CpG ODNs, activation of the kinase is a prerequisite for the delivery of CpG into TLR9-containing endolysosomes and for the CpG-induced up-regulation of TLR9 expression. Our results reveal an alternative, Syk-dependent pathway of CpG-induced B cell stimulation, which is initiated at the plasma membrane and seems to be an upstream requirement for endosomal TLR9-driven B cell proliferation and differentiation.

Original languageEnglish
Pages (from-to)2223-2236
Number of pages14
JournalCellular and Molecular Life Sciences
Volume72
Issue number11
DOIs
Publication statusPublished - Jun 1 2015

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Keywords

  • B cells
  • Cell activation
  • Signal transduction
  • Syk
  • TLR9

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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