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 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.
Cohen-Sfady
Michal
M
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Nussbaum
Gabriel
G
Pevsner-Fischer
Meirav
M
Mor
Felix
F
Carmi
Pnina
P
Zanin-Zhorov
Alexandra
A
Lider
Ofer
O
Cohen
Irun R
IR
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D018834:Chaperonin 60 / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D018834:Chaperonin 60; D000949:Histocompatibility Antigens Class II; D007378:Interleukins; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4