UNEXPECTEDLY HIGH OCCURRENCE OF CATALYTIC ANTIBODIES IN MRL/LPR AND SJL MICE IMMUNIZED WITH A TRANSITION-STATE ANALOG - IS THERE A LINKAGE TO AUTOIMMUNITY

Upon testing the ability of several strains of mice to elicit esterolytic antibodies after immunization with a p-nitrobenzyl phosphonate hapten, we have found that the occurrence of catalytic antibodies in SJL and MRL/lpr autoimmune mice is dramatically higher than in normal mouse strains (e,g., the wild-type MRL/++ or BALB/c). Fewer than 10 catalytic clones are usually obtained from a single fusion of lymphocytes taken from normal mice, whereas several hundred catalytic clones are obtained in SJL or MRL/lpr mice. Differences in the numbers of hapten-binding clones do not account for the high occurrences of catalytic clones in these strains, This phenomenon prevailed in the early responses; in both SJL and MRL/lpr mice a significant decline in the appearance of catalytic clones was observed after multiple immunizations, Esterolytic antibodies were not found in MRL/lpr mice immunized with haptens that do not mimic the transition state for the hydrolysis of the ester substrate (e,g., with a substrate analog). The catalytic antibodies manifest high specificity to the antigen and variability in their binding and catalytic properties. The use of autoimmunity-prone mice may greatly expand the repertoire of catalytic clones elicited against a transition-state analog hapten. More intriguing is the possible linkage between autoimmunity and the appearance of catalytic antibodies. These results suggest that there is normally a selection against the expression of certain variable genes encoding antibodies with catalytic activity.