Apoptotic Death of Antigen-Carrying, Effete Promote Tolerance Induction by Eliciting Ligand-Expressing Invariant NK T Cells Oral Nickel Tolerance: Fas

Whereas oral nickel administration to C57BL/6 mice (Ni high mice) renders the animals tolerant to immunization with NiCl 2 combined with H 2 O 2 as adjuvant, as determined by ear-swelling assay, it fails to tolerize J␣18 ؊/؊ mice, which lack invariant NKT (iNKT) cells. Our previous work also showed that Ni high splenic B cells can adoptively transfer the nickel tolerance to untreated (Ni low) recipients, but not to J␣18 ؊/؊ recipients. In this study, we report that oral nickel administration increased the nickel content of splenic Ni high B cells and up-regulated their Fas expression while down-regulating expression of bcl-2 and Bcl-x L , thus giving rise to an Ag-carrying, apoptosis-prone B cell phenotype. Although oral nickel up-regulated Fas expression on B cells of both wild-type Ni high and J␣18 ؊/؊ Ni high mice, only the former showed a reduced number of total B cells in spleen when compared with untreated, syngeneic mice, indicating that iNKT cells are involved in B cell homeostasis by eliciting apoptosis of effete B cells.