Functional analysis of Toxoplasma gondii-derived HSP70 functions as a B cell mitogen

Toxoplasmagondii-derived heat shock protein 70 (T.g.HSP70) induced prominent proliferation in splenic B cells derived from not only T. gondii-infected but also uninfected mice. Nude mice responded to T.g.HSP70, but SCID and RAG1(-/-)B6 mice failed to respond. B220(+) but neither CD4(+) nor CD8(+) population of spleen cells responded. Polymyxin B, a potent inhibitor of lipopolysaccaride (LPS), did not eliminate T.g.HSP70-induced proliferation. C3H/HeJ mice carrying a point mutation in the cytoplasmic region of TLR4 molecule, failed to respond to T.g.HSP70 while C3H/HeN mice responded. The involvement of TLR4 molecule in T.g.HSP70-induced proliferative responses of spleen cells was confirmed by the use of TLR4(+) mice. On the other hand, T.g.HSP70-induced spleen cell proliferation was observed in MyD88(-/-) mice, suggesting the participation of MyD88(-/-) independent pathway in the downstream of TLR4 molecules in T.g.HSP70-induced proliferative responses, although the involvement of MyD88 in host defense of T. gondii -infected mice has been observed.