An inherent hemagglutinin-specific immunoglobulin lambda light chain bias in the ferret de novo response to influenza A and B virus infections 2985

Description The domestic ferret (M. putorius furo) is used in laboratories studying the influenza virus due to their human-like expression of α2,6-linked terminal sialic acid residues, but their immune response to the virus remains understudied. In this presentation, we further analyze the hemagglutinin (HA)-specific immunoglobulin (Ig) λ bias previously described after primary influenza A virus (IAV) infections in ferrets. ELISA and ELSPOT were used to dissect the Igλ and Igκ antibody and cellular responses after primary and secondary influenza virus infections. While the Igλ bias to the whole HA is present in the serum and antibody-presenting cells (APC) after a primary infection with H1N1 IAV, we find that the HA-stem antibody response has an Igκ bias 14 to 28 days post-infection (DPI). The H1 HA-stem response is further boosted after a secondary H1N1 IAV infection and continues to display the Igκ bias at 14 DPI, while the whole HA-binding has a balance of Igλ to Igκ. Interestingly, an Igλ bias was present after the secondary infection in the APC at 7 DPI. The HA-stem Igκ bias is nonexistent in an H3N2 IAV and IBV primary infections, but the whole HA-specific Igλ bias was observed in the serum 7 to 28 DPI and in the APC 7 to 10 DPI. In conclusion, these data suggest that the H1 stem-directed Igκ bias may develop from an epitope-directed mechanism, while the whole-HA Igλ bias is directed by a unique mechanism in ferrets where de novo antibody responses have an inherent Igλ bias. Funding Sources NIH 75N93019C00052 Topic Categories Veterinary and Comparative Immunology (VET)