Unexpectedly high occurrence of catalytic antibodies in MRL/lpr and SJL mice immunized with a transition-state analog: is there a linkage to autoimmunity?

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-03, Vol.92 (6), p.2145-2149
• Main Authors: Tawfik, D S, Chap, R, Green, B S, Sela, M, Eshhar, Z
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - metabolism; Antibody Formation; Autoimmune Diseases - immunology; Autoimmunity; Binding, Competitive; Catalysis; Catalysts; Clone Cells; Crosses, Genetic; Enzyme-Linked Immunosorbent Assay; Haptens; Immunity (Disease); Lymphocytes - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Mutant Strains; Rodents; Species Specificity
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.6.2145

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.