Comparison of Igκ and Igλ binding toward influenza virus hemagglutinin and SARS-CoV-2 Spike protein during primary viral infections in humans, mice, and pigs.

An Igλ light chain bias (IgL) has been identified in ferrets after a primary influenza virus infections. To further study if this phenotype is consistent between species, serum immunoglobulin Igλ and Igκ light chain (IgL) prevalence was evaluated in humans, mice, and pigs following a primary respiratory virus infection. Each IgL population was tested for its binding capacity to the immunodominant viral glycoprotein of the infecting virus. Humans infected with their initial SARS-CoV-2 virus infection had a marginal Igκ bias against the spike (S) glycoprotein, but had no observable IgL bias toward the receptor binding domain of the S protein. Mice had an Igκ bias against the influenza virus hemagglutinin (HA) after a primary infection with an H1N1 or H3N2 influenza virus. Conversely, pigs had an Igλ bias to the HA after a primary infection with either influenza virus subtype. These results highlight that IgL biases vary in different species after a primary viral respiratory infection. Overall, these results have implications for how immunological data should be interpreted between species and the selection of animal models for various applications.