Heat Shock Protein 60 Activates B Cells via the TLR4-MyD88 Pathway

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 Escherich...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2005-09, Vol.175 (6), p.3594-3602
Main Authors: Cohen-Sfady, Michal, Nussbaum, Gabriel, Pevsner-Fischer, Meirav, Mor, Felix, Carmi, Pnina, Zanin-Zhorov, Alexandra, Lider, Ofer, Cohen, Irun R
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - deficiency
Adaptor Proteins, Signal Transducing - metabolism
Animals
Antigens, Differentiation - metabolism
B-Lymphocytes - immunology
Cell Proliferation
Chaperonin 60 - immunology
Escherichia coli
Histocompatibility Antigens Class II - genetics
Humans
Interleukins - metabolism
Lymphocyte Activation - immunology
Mice
Mice, Inbred Strains
Mice, Knockout
Myeloid Differentiation Factor 88
Receptors, Immunologic - deficiency
Receptors, Immunologic - metabolism
Signal Transduction - immunology
Toll-Like Receptor 4 - deficiency
Toll-Like Receptor 4 - metabolism
Up-Regulation - genetics
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Summary: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-gamma 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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.175.6.3594