Heterosubtypic immunity to influenza A virus infection requires B cells but not CD8(+) cytotoxic T lymphocytes

Heterosubtypic immunity (HSI), defined as protective cross-reactivity to le thal infection with influenza A virus of a serotype different from the viru s initially encountered, is thought to be mediated by cross-reactive cytoto xic T lymphocytes (CTL). This study provides direct evidence for the role o f effector CTL versus B cells in HSI in mice with a targeted disruption in the a chain of CD8 molecule (CD8(+) T cell deficient) or the immunoglobulin mu heavy chain (B cell deficient), respectively. CD8(+) T cell-deficient m ice developed complete HSI. These mice displayed normal humoral immune resp onses, as determined by titers of subtype cross-reactive antibodies and vir us-neutralizing antibodies specific for the immunizing influenza strain. In contrast, HSI was not observed in B cell-deficient mice, although these mi ce could mount cross-reactive CTL responses. These results show that B cell s are required for HSI and provide new insight into the mechanisms of HSI, with significant implications in vaccine development.