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Primed lymphoid cell tolerance. II. In vivo tolerization of highly tolerogen-sensitive hapten-primed, potentially
The relative ease of tolerizing IgM-bearing versus IgG-bearing B cells was investigated. Previous work had shown that IgG-bearing trinitrophenyl (TNP)-specific B cells from mice primed and boosted with TNP-keyhole limpet hemocyanin (TNP-KLH) are highly susceptible to tolerization in vitro by TNP presented on an unrelated carrier. TNP-OVA was used as tolerogen, as it may represent a more general class of tolerogens than those which are nonmetabolizable or immunoglobulin containing. This study showed that highly primed B cells are tolerizable in vivo using TNP-OVA, with the IgG response to TNP-KLH easier to tolerize than the IgM response. To determine if the ease of tolerization of the IgG response in vivo was due to intrinsic differences in B-cell precursors of the IgM and IgG responses, tolerance was performed in vitro with B cells of defined surface isotypes. A T-independent antigen, TNP-endotoxin, was employed to minimize T-cell effects. At least 10 times as much TNP-OVA was required to tolerize B cells bearing the IgM surface isotype than those with the IgG surface isotype. Thus, the ease of inhibition of the IgG response as compared to the IgM response in vivo by preexposure to TNP-OVA may be at least partially explained by inherent differences in IgM and IgG B-cell precursors.
The relative ease of tolerizing IgM-bearing versus IgG-bearing B cells was investigated. Previous work had shown that IgG-bearing trinitrophenyl (TNP)-specific B cells from mice primed and boosted with TNP-keyhole limpet hemocyanin (TNP-KLH) are highly susceptible to tolerization in vitro by TNP presented on an unrelated carrier. TNP-OVA was used as tolerogen, as it may represent a more general class of tolerogens than those which are nonmetabolizable or immunoglobulin containing. This study showed that highly primed B cells are tolerizable in vivo using TNP-OVA, with the IgG response to TNP-KLH easier to tolerize than the IgM response. To determine if the ease of tolerization of the IgG response in vivo was due to intrinsic differences in B-cell precursors of the IgM and IgG responses, tolerance was performed in vitro with B cells of defined surface isotypes. A T-independent antigen, TNP-endotoxin, was employed to minimize T-cell effects. At least 10 times as much TNP-OVA was required to tolerize B cells bearing the IgM surface isotype than those with the IgG surface isotype. Thus, the ease of inhibition of the IgG response as compared to the IgM response in vivo by preexposure to TNP-OVA may be at least partially explained by inherent differences in IgM and IgG B-cell precursors.