Heat Shock Protein 60, via MyD88 Innate Signaling, Protects B Cells from Apoptosis, Spontaneous and

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-xL, and survivin, maintenance of the mitochondrial transmembrane po-tential, 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. The Journal of Immunology, 2009, 183: 890–896. T he adaptive immune response is regulated, among otherfactors, by a balance between the proliferation of acti-vated immune cells and their death. Apoptosis is required both to terminate the adaptive immune response and to regulate lymphocyte maturation and selection (1, 2). The balance between activation signals, apoptosis-inducing signals, and survival signals is notable in B cells. Mature B cells undergo spontaneous apopto-sis in vitro, and their survival requires cytokines or antigenic stim-ulation (3, 4). B cell activation by anti-IgM Ab induces B cel