Delineation of the antibody light chain biases and kinetics following primary and secondary influenza virus infections of ferrets.

Abstract

The ferret is considered the "gold standard" animal model for influenza virus research. However, the mechanisms of the ferret humoral immune responses remain understudied. Here, the kinetic profile of the influenza A or B virus hemagglutinin (HA)-specific primary antibody response was tracked until the contraction phase. Additionally, the acute humoral response following a secondary infection with a homosubtypic H1N1 influenza A virus was evaluated. In particular, the HA-binding reactivity in serum was quantified and the number of HA-specific antibody-secreting cells was evaluated in different immune compartments, including peripheral blood mononuclear cells, spleen, and mediastinal lymph nodes at multiple time points postinfection. Differences in Igκ and Igλ light chain (IgL) usage within the elicited HA-specific antibody response was observed after primary and secondary influenza virus infection. Ferrets had de novo humoral immune responses that were detected approximately 7 to 10 days following influenza virus infection with an inherent Igλ serum antibody bias directed toward the HA head domain, with detectable hemagglutination inhibition activity. The Igλ bias was also extended to influenza B virus primary infections. Higher serum Igκ reactivity was detected following secondary influenza virus infection compared to the primary viral infection, which was directed toward the conserved H1 stem domain. Taken together, our findings confirm inherent IgL biases in the anti-HA antibody response expressed following influenza virus primary and secondary infections that result in a unique profile of antibody functional activity.