Intact Antiinfluenza Virus Immune Response in Targeted κ-Deficient Mice

Abstract

Immunoglobulins are encoded by genes located in three different loci, the heavy chain (IgH), κ light chain (Igκ), and λ light chain (Igκ) loci. In mice, the κ/λ ratio of B cells is 95:5. In a previous study, we reported that κ gene deletion causes the alternative usage of λ₁ (93%) and λ₂ (7%) light chains, and that the κ anti-TNP repertoire is compensated for by the λ repertoire even though the latter is clonally restricted in K−/− mice. To investigate the contribution of λ antibodies to protection against virus, we compared K−/− mice with 129/Sv wild-type mice with respect to immune responses to influenza virus. PR8 virus immunized K−/− and 129/Sv mice showed no difference in the titer of anti-HA antibodies. Furthermore, the same immunized mice had sufficiently high neutralizing antibody titer to prevent infection when challenged with 7.5 × 10⁴ TCID₅₀ of PR8 virus. In addition, immunized K−/− mice were resistant to infection with 7.5 × 10⁴ TCID₅₀ and 7.5 × 10⁵ TCID₅₀ (10 and 100 LD₅₀, respectively) of PR8 virus. Finally, K−/− mice are also capable of inducing cytotoxic T cells. These results suggest that the λ repertoire can compensate for the κ repertoire by generating a fully protective neutralizing antibody response.