Heat shock protein 60 activates B cells via the TLR4-MyD88 pathway

Michal Cohen-Sfady, Gabriel Nussbaum, Meirav Pevsner-Fischer, Felix Mor, Pnina Carmi, Alexandra Zanin-Zhorov, Ofer Lider, Irun R. Cohen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

168 Scopus citations

Abstract

We recently reported that soluble 60-kDa heat shock protein (HSP60) can directly activate T cells via TLR2 signaling to enhance their Th2 response. In this study we investigated whether HSP60 might also activate B cells by an innate signaling pathway. We found that human HSP60 (but not the Escherichia coli GroEL or the Mycobacterial HSP65 molecules) induced naive mouse B cells to proliferate and to secrete IL-10 and IL-6. In addition, the HSP60-treated B cells up-regulated their expression of MHC class II and accessory molecules CD69, CD40, and B7-2. We tested the functional ability of HSP60-treated B cells to activate an allogeneic T cell response and found enhanced secretion of both IL-10 and IFN-γ by the responding T cells. The effects of HSP60 were found to be largely dependent on TLR4 and MyD88 signaling; B cells from TLR4-mutant mice or from MyD88 knockout mice showed decreased responses to HSP60. Care was taken to rule out contamination of the HSP60 with LPS as a causative factor. These findings add B cells to the complex web of interactions by which HSP60 can regulate immune responses.

Original languageAmerican English
Pages (from-to)3594-3602
Number of pages9
JournalJournal of Immunology
Volume175
Issue number6
DOIs
StatePublished - 15 Sep 2005

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