Antibody response against poly (Glu60Ala30Tyr10) terpolymer and bacterial levan in kappa-deficient mice.

Abstract

In murine species, the kappa (+)-bearing immunoglobulins dominate the antibody (Ab) repertoire with a kappa/lambda ratio of 95:5. The aim of the present study is to investigate the characteristics of the antibody response in kappa-deficient (K-/-) mice immunized with a T-dependent synthetic antigen, poly(Glu60Ala30Tyr10) (GAT) and a T-independent antigen, bacterial levan (BL). K-/- mice were obtained by targeted 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, although 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 are detected neither in wild-type nor in K-/- mice. Like kappa + Ab, the majority of lambda 1+ mAb are specific for beta 2-6 fructosan present in BL and rye levan and, to some extent, express the BL-specific idiotype, A48ld. Our results show that important compensatory mechanisms occur in kappa-deficient mice, restoring their ability to mount immune responses against a variety of T-dependent and T-independent antigens by the alternative usage of the clonally restricted lambda repertoire.