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The murine B cell repertoire responsive to an influenza-infected syngeneic cell line.

The conditions for eliciting monoclonal B cell responses to an influenza-infected syngeneic tumor cell line were defined. Although the infected tumor cell stimulated vigorous responses, few clones recognized tumor antigens, whereas over 90% of the monoclonal antibodies recognized viral antigens expressed on the surface of infected tumor cells. Approximately one-third of the virus-specific antibodies reacted with the viral hemagglutinin (HA) or neuraminidase, and the remainder recognized antigens found on the surface of infected cells but not on the virion or uninfected cells. The majority of the antibodies reactive with the virion recognized HA determinants, whereas few reacted with the neuraminidase. Subsequent analysis revealed that most neuraminidase determinants exposed on the intact virion were not available on the surface of infected cells. In contrast, the majority of the HA determinants expressed on the virion were also available on the surface membranes of infected cells, and a highly diverse set of antibodies recognized the HA expressed either on the virion or on the infected cell surface. Finally, differences were noted in the heavy chain isotype of antibodies produced in response to infected cells vs purified virus. A majority of monoclonal responses to purified influenza virus included IgA antibodies, whereas responses to infected cells showed less IgA and a concomitant increase in clones expressing IgG.