SUPERSTIMULATORY INFLUENZA-VIRUS AND HIGHLY ORGANIZED BCR-LIGANDS ACTSYNERGISTICALLY ON B-CELL ACTIVATION

The influenza virus glycoprotein hemagglutinin (HA) behaves as a super stimulatory protein for B lymphocytes from various species. Polyclonal B cell stimulation mediated by HA can be blocked by soluble anti-Ig a ntibodies. We here report that,if presented in a highly organized form , i.e., as anti-Ig mAb coupled to dextran (anti-Ig-Dex), conventional BCR-ligands and influenza viruses act synergistically on murine B cell activation. Proliferative responses of both spellen-derived and perit oneal B cells mediated by suboptimal amounts of HA were significantly augmented by costimulation with anti-Ig-Dex, and vice versa. Similarly , anti-Ig-Dex, which on its own cannot incude Ig production in the abs ence of added cytokines, significantly enhanced Ig synthesis in respon se to superstimulatory HA. By contrast, poorly organized BCR-ligands ( i.e. the same anti-Ig mAb in a soluble form) had either no, or a stron g inhibitory effect on virus-triggered lymphocyte activation. Assays w ith various second messenger-antagonists, however, revealed clear diff erences in the signaling pathway employed by anti-Ig-Dex and HA, sugge sting that the functional synergy between the two multimeric agents is mediated by engagement of distinct transducing elements. Taken togeth er, these results indicate that the superstimulatory function of influ enza virus HA represents a molecular strategy to mimick B cell activat ion by conventional, highly organized particulate-antigens.