ANTIBODY-RESPONSE AGAINST POLY (GLU(60)ALA(30)TYR(10)) TERPOLYMER ANDBACTERIAL LEVAN IN KAPPA-DEFICIENT MICE

In murine species, the kappa(+)-bearing immunoglobulins dominate the a ntibody (Ab) repertoire with a kappa/lambda ratio of 95:5. The aim of the present study is to investigate the characteristics of the antibod y response in kappa-deficient (K-/-) mice immunized with a T-dependent synthetic antigen, poly (Glu(60)Ala(30)Tyr(10)) (GAT) and a T-indepen dent antigen, bacterial levan (BL). K-/- mice were obtained by targete d deletion of the J kappa C kappa gene segments. In response to GAT, K -/- mice respond by producing increasing amounts of anti-GAT Ig lambda 1 and Ig lambda 2 in the primary as well as secondary response, altho ugh anti-GAT specific monoclonal antibodies (mAb) raised in K-/- mice are mostly of IgM isotype. The GAT public idiotype, GATIdX, present on all GAT-specific Ab bearing kappa light chain, is not detected in the sera of K-/- mice or on any of the anti-GAT lambda 1 mAb. In response to BL, the amount of Ig lambda 1(+) Ab in K-/- mice is comparable to the amount of Ig kappa(+) Ab in normal mice. However, lambda 2(+) Ab a re detected neither in wild-type nor in K-/- mice. Like kappa(+) Ab, t he majority of lambda 1(+) mAb are specific for beta 2-6 fructosan pre sent in BL and rye levan and, to some extent, express the BL-specific idiotype, A48ld. Our results show that important compensatory mechanis ms occur in kappa-deficient mice, restoring their ability to mount imm une responses against a variety of T-dependent and T-independent antig ens by the alternative usage of the clonally restricted lambda reperto ire.