ANTIBODY-RESPONSE ELICITED BY T-DEPENDENT AND T-INDEPENDENT ANTIGENS IN GENE TARGETED KAPPA-DEFICIENT MICE

Animal models substantially contribute to the understanding of the pat hogenesis of various human diseases, including those associated with g enetic defects, Our study investigated the characteristics of antibody responses elicited by T-dependent and T-independent antigens in mice rendered kappa-deficient by targeted deletion of the J(kappa)C(kappa) gene segments. It is known that in normal murine species the kappa rep ertoire dominates the antibody repertoire (kappa/lambda ratio = 95:5), Our results indicate that the kappa gene deletion causes the alternat ive usage of lambda 1 (93%) and lambda 2 (7%) light chains, confirming previous studies demonstrating that in kappa-deficient mice all B cel ls express Ig lambda receptors, The anti-trinitrophenylbenzene (TNP) r esponse in K-/- mice was compensated for by hi and lambda 2 bearing Ig s, However, isoelectric focusing analysis of anti-TNP antibodies showe d a considerably more restricted pattern of lambda anti-TNP antibodies in K-/- as compared with kappa antibodies in normal mice, No major di fferences were observed in the affinity for the hapten of kappa or lam bda 1 or lambda 2 mAbs obtained from 129/Sv and K-/- mice. Furthermore , lambda 1 and lambda 2 chains can reconstitute the expression of an i diotype (4601d) borne on kappa anti-TNP antibodies, The 460ld was dete cted both in polyclonal and monoclonal anti-TNP antibodies obtained fr om K-/- mice, Our results clearly showed that the kappa anti-TNP reper toire is compensated by the lambda repertoire even though the latter i s clonally restricted in K-/- mice.