A proliferation inducing ligand (APRIL) is implicated in the regulation of class switch recombination to IgA in T-independent B cell responses. Since B cells play an important role in the immunity to influenza A virus and resistance against the virus is partly controlled by T-independent IgA B cell responses, we studied the role of APRIL during an influenza A infection in vivo. APRIL transgenic, wild-type and APRIL deficient mice were intranasally infected with a non-lethal dose of a mouse adapted strain of influenza A. Compared to wild-type mice, APRIL deficient mice showed a twofold reduction in the amount of macrophages in the lungs and a tendency towards decreased granulocyte influx in the early leukocyte recruitment phase. Although the T cell immune response against influenza was unaffected, APRIL Tg mice showed prolonged influenza-specific IgM production and differential class switching. Unexpectedly, the IgA B cell response was completely T helper cell dependent and also not affected by the absence or presence of APRIL. In addition, viral clearance and recovery from the infection was not influenced by APRIL. Combined these results indicate that APRIL affects specific aspects of the anti-influenza response, but plays a limited role in disease recovery.