Although rheumatoid factor-like IgM (Rf-like) has been demonstrated to augment the effect of parasite-specific IgG in vitro, the in vivo role of RF-like IgM in parasite is less clear. Understanding the mechanisms involved in augmentation of parasite immunity by RF-like IgM is central to the possible therapeutic use of RF-like IgM's to aid in the control of malarial parasitemia. The long term objective of this proposal is to elucidate the specific contribution(s) of RF-like in immunity to malarial infection. The immediate objective of this study is to determine the relationship(s) among antigen location on parasite substructures, parasite-specific IgG subisotype, and RF-like IgM subisotypes specificity in augmentation of immunity to Plasmodium berghei in Balb/c mice. The experimental design will incorporate the passive transfer of infection-induced, parasite-specific IgG and Rf-like IgM and monoclonal parasite-specific IgG and RF-like IgM to evaluate the contributions of the above factors to resistance.
The Specific Aims established to achieve this objective are 1) to determine the parameters for enhancement of 2) to develop monoclonal RF-like IgM's of differing subisotypic specific for epitopes expressed on various parasite substructures, and 3) to evaluate the contribution(s) of antigen location, IgG subisotype, and RF-like subisotype specificity to resistance by the passive transfer of these monoclonal antibodies into P. berghei-infected Balb/c mice.
