Improved generation of catalytic antibodies by MRL/MPJ- lpr/ lpr autoimmune mice

Abstract

To compare the abilities of different strains of mice to elicit catalytic antibodies (Abs), we determined the occurrence of esterolytic Abs in BALB/c (normal strain) and MRL/MPJ- lpr/lpr (MRL/ lpr, autoimmune) mice after immunization with the transition state analog (TSA) 1. Hybridoma supernatants elicited against TSA 1 were screened by ELISA for binding to the BSA-conjugated TSA 1 (= 3b), and then screened for binding to the BSA-linked short TSA 2 (= 4). We obtained eight times more positives from MRL/ lpr mice than from BALB/c mice by these screening steps. The monoclonal antibodies (mAbs) obtained here were examined for binding and catalytic activity. Fifteen of 25 mAbs from MRL/ lpr had esterolytic activity, compared with only two of 21 mAbs from BALB/c. These results demonstrated that the occurrence of catalytic Abs was much higher in MRL/ lpr mice than in BALB/c mice, which is in good agreement with the previous report by Tawfik et al. [Tawfik, D.S., Chap, R., Green, B.S., Sela, M., Eshhar, Z., 1995. Proc. Natl. Acad. Sci. U.S.A. 92, 2145–2149] using a different kind of TSA. Thus, these studies strongly suggest that using the appropriate strain can be a key factor in the efficient production of catalytic Abs. Furthermore, these mAbs were characterized to elucidate the mechanism of strain difference, and determine whether MRL/ lpr mice can be used with other TSAs for the efficient production of catalytic Abs.