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), kappa light chain (Ig kappa), and lambda light chain (Ig lambda) loci. In mice, the kappa/lambda ratio of B cells is 95:5. In a previous study, we reported that kappa gene deletion causes the alternative usage of lambda 1 (93%) and lambda 2 (7%) light chains, and that the kappa anti-TNP repertoire is compensated for by the lambda repertoire even though the latter is clonally restricted in K-/- mice. To investigate the contribution of lambda 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 x 10(4) TCID50 of PR8 virus. In addition, immunized K-/- mice were resistant to infection with 7.5 x 10(4) TCID50 and 7.5 x 10(5) 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 lambda repertoire can compensate for the kappa repertoire by generating a fully protective neutralizing antibody response.

Protective Cellular Immunity Against Influenza Virus Induced by Plasmid Inoculation of Newborn Mice

“…After adding DMEM-10% FCS, the plates were incubated for 48 hrs at 37C and 5% CO2. Supernatants were harvested and coincubated for 30 min at room temperature with a suspension of 0.5% chicken red blood cells in 96-well round-bottom flexible plates (Falcon) as previously described (Isobe et al, 1994). Virus titers were estimated by interpolation of the dilution that showed hemagglutination in 50% of wells (Reed and Muench, 1938).…”

The Primary Antibody Repertoire of κ‐Deficient Mice is Characterized by Non‐Stochastic Vλ1 + VH Gene Family Pairings and a Higher Degree of Self‐Reactivity

“…In addition, evidence for positive selection, revealed by restricted V H þ V L pairing in the available l B-cell repertoire, exists [31]. Furthermore, V l genes have been observed to effectively reconstitute the immune response to influenza virus by developing neutralizing antibodies in JC k D mice [39] and, also, to other thymus dependent and independent antigens [32,40]. The experiments outlined here demonstrate the ability of an exclusively l-light-chain-expressing peripheral B-cell repertoire to generate NAAb specificities in the circulating immunoglobulin pool, although at higher levels (probably as a result of endogenous selection processes on the available restricted germline diversity).…”

Noncoding RNA danger motifs bridge innate and adaptive immunity and are potent adjuvants for vaccination

“…Virus titers were measured by 48-hour incubation of serial dilutions of samples with permissive MDCK cells, followed by standard hemagglutination with chicken red blood cells (Animal Technologies Inc., Tyler, Texas, USA). The endpoint titers were estimated in triplicate measurements by interpolation (15) and expressed as total TCID 50 /organ. Measurement of antibody and T cell response.…”