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

To compare the abilities of different strains of mice to elicit catalytic a ntibodies (Abs), we determined the occurrence of esterolytic Abs in BALB/c (normal strain) and MRL/MPJ-lpr/lpr (MRL/lpr, autoimmune) mice after immuni zation with the transition state analog (TSA) 1. Hybridoma supernatants eli cited against TSA 1 were screened by ELISA for binding to the BSA-conjugate d 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) obta ined here were examined for binding and catalytic activity. Fifteen of 25 m Abs from MRL/lpr had esterolytic activity, compared with only two of 21 mAb s 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 a greement 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 sug gest 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/lp r mice can be used with other TSAs for the efficient production of catalyti c Abs. (C) 2000 Elsevier Science B.V. All rights reserved.