Hyperimmunization alters Fc gamma antigenicity. Linkage to glycosylation

Rabbits were hyperimmunized with streptococcal vaccine to produce hyperimmune (HI) IgG, and both HI IgG and autologous preinoculation (PI) IgG were used to prepare Fc gamma. mAb raised against these, and deglycosylated PI Fc gamma preparations were subsequently used to determine if antigenic differences existed between autologous HI and PI Fc gamma. Although the majority of mAb examined did not discriminate between the two sources of Fc gamma, several mAb exhibited remarkable specificity for autologous HI Fc gamma. We did not detect any mAb which exhibited the converse specificity. Of the mAb chosen for study, all except one appeared specific for determinants located in C gamma 2; the exception specifically reacted with pFc', and did not discriminate between the two Fc preparations. Importantly, partial deglycosylation of autologous PI Fc gamma led to equivalent reactivity with previously HI-specific mAb. The results of this study provide immunologic evidence that abnormal C gamma 2 structures exist prior to and reach serologically detectable levels during the hyperimmune response in these animals, apparently as a result of glycosylation pattern alterations within the Fc region. Such autoantigenic differences could account for the induction of RF under these conditions, and perhaps in certain human arthritic diseases as well.