Antibody response elicited by T-dependent and T-independent antigens in gene targeted κ-deficient mice

Animal models substantially contribute to the understanding of the pathogenesis of various human diseases, including those associated with genetic defects. Our study investigated the characteristics of antibody responses elicited by T-dependent and T-independent antigens in mice rendered k-deficterrt by targeted deletion of the J_kC_k gene segments. It is known that in normal murine species the k repertoire dominates the antibody repertoire (k/λratio = 95:5). Our results indicate that the k gene deletion causes the alternative usage of λ1 (93%) and λ2 (7%) light chains, confirming previous studies demonstrating that in k-deficlent mice all B cells express IGλ receptors. The anti-trinitrophenylbenzene (TUP) response in K-/- mice was compensated for by α1 and α2 bearing Igs. However, isoelectric focusing analysis of anti-TNP antibodies showed a considerably more restricted pattern of α anti-TNP antibodies in K-/- as compared with κ antibodies in normal mice. No major differences were observed in the affinity for the hapten of κ orα1 or α2 mAbs obtained from 129/Sv and K-/- mice. Furthermore, κ1 and κ2 chains can reconstitute the expression of an Idiotype (460ld) borne on κ anti-TNP antibodies. The 460ld was detected both in polyclonal and monoclonal anti-TNP antibodies obtained from K-/- mice. Our results clearly showed that the κ anti-TNP repertoire is compensated by the α repertoire even though the latter is clonally restricted in K-/- mice.