FcRIIB modulates splenic germinal center response against immune subversion during acute influenza A virus infection

Background: B cells are essential for providing humoral protection against acute influenza A virus (IAV) infection. FcyRIIB, a regulator of antibody (Ab) production, influences immune responses during pathogen infections, but its specific impact on humoral protection and B cell-mediated responses against IAV remains unclear. Methods: To investigate FcyRIIB's role in host defense and B cell function during acute IAV infection, we generated mice with systemic FcyRIIB deficiency, functional impairment, and B cell-specific FcyRIIB deletion. We infected these mice with PR8 (H1N1) or Hkx31 (H3N2) IAVs and evaluated body weight preservation, survival rates, Ab production, viral neutralization, Ab affinity maturation, and germinal center B cell development. Results: Mice lacking FcyRIIB or with impaired function showed improved protection, preserved body weight, and increased survival rates during IAV infection. Notably, mice with haploinsufficient FcyRIIB function displayed protective effects. Selective deficiency of FcyRIIB in B cells led to enhanced Ab production, resulting in elevated IAV-specific Abs in the serum with superior viral neutralizing potency. However, the impact on the affinity maturation index of virus-specific Abs was modest. Accordingly, FcyRIIB-deficient B cells maintained normal germinal center B cell development during IAV infection, whereas wild-type mice exhibited delayed differentiation. Conclusion: Our research underscores the pivotal role of FcyRIIB in host defense and B cellmediated immunity during acute IAV infection. Additionally, our discoveries hold implications for antiviral treatments, particularly during the initial stages of IAV infection, aimed at enhancing the host's humoral immune response.