The antibody response to
influenza infection is largely dependent on CD4 T cell help for B cells. Cognate signals and secreted factors provided by CD4 T cells drive B cell activation and regulate antibody isotype switching for optimal
antiviral activity. Recently, we analyzed
HLA-DR1 transgenic (DR1) mice and C57BL/10 (B10) mice after
infection with influenza virus A/New Caledonia/20/99 (NC) and defined
epitopes recognized by virus-specific CD4 T cells. Using this information in the current study, we demonstrate that the pattern of secretion of
IL-2, IFN-γ, and
IL-4 by CD4 T cells activated by NC
infection is largely independent of
epitope specificity and the magnitude of the
epitope-specific response. Interestingly, however, the characteristics of the virus-specific CD4 T cell and the B cell response to NC
infection differed in DR1 and B10 mice. The response in B10 mice featured predominantly IFN-γ-secreting CD4 T cells and strong
IgG2b/IgG2c production. In contrast, in DR1 mice most CD4 T cells secreted
IL-2 and
IgG production was IgG1-biased.
Infection of DR1 mice with
influenza PR8 generated a response that was comparable to that in B10 mice, with predominantly IFN-γ-secreting CD4 T cells and greater numbers of IgG2c than
IgG1 antibody-secreting cells. The response to intramuscular vaccination with inactivated NC was similar in DR1 and B10 mice; the majority of CD4 T cells secreted
IL-2 and most
IgG antibody-secreting cells produced
IgG2b or IgG2c. Our findings identify inherent host influences on characteristics of the virus-specific CD4 T cell and B cell responses that are restricted to the lung environment. Furthermore, we show that these host influences are substantially modulated by the type of infecting virus via the early induction of innate factors. Our findings emphasize the importance of immunization strategy for demonstrating inherent host differences in CD4 T cell and B cell responses.