Heat shock protein 60, via MyD88 innate signaling, protects B cells from apoptosis, spontaneous and induced.
We recently reported that heat shock protein 60 (HSP60) via TLR4 signaling activates B cells and induces them to proliferate and secrete IL-10. We now report that HSP60 inhibits mouse B cell apoptosis, spontaneous or induced by dexamethasone or anti-IgM activation. Unlike HSP60 enhancement of B cell proliferation and IL-10 secretion, TLR4 signaling was not required for the inhibition of apoptosis by HSP60; nevertheless, MyD88 was essential. Inhibition of apoptosis by HSP60 was associated with up-regulation of the antiapoptotic molecules Bcl-2, Bcl-x(L), and survivin, maintenance of the mitochondrial transmembrane potential, and inhibition of caspase-3 activation. Moreover, B cells incubated with HSP60 manifested prolonged survival following transfer into recipient mice. These results extend the varied role of HSP60 in the innate regulation of the adaptive immune response.
Cohen-Sfady
Michal
M
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Pevsner-Fischer
Meirav
M
Margalit
Raanan
R
Cohen
Irun R
IR
D000818:Animals; D000917:Antibody Formation; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology* / Q000637:transplantation; D061945:Caspase Inhibitors; D002470:Cell Survival; D017690:Cell Transplantation; D018834:Chaperonin 60 / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D007075:Immunoglobulin M / Q000276:immunology; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D061945:Caspase Inhibitors; D018834:Chaperonin 60; D007075:Immunoglobulin M; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D003907:Dexamethasone