The polyclonal B-cell-activating property of protein A is not due to its interaction with the FC part of immunoglobulin receptors.

Protein A from Staphylococcus aureus bacteria was found to be a B-cell mitogen and a potent polyclonal B-cell activator (PBA) of antibody synthesis for murine lymphocytes in the absence of macrophages or T lymphocytes. It did not activate T lymphocytes. We investigated whether the interaction between protein A and the Fc part of Ig molecules was responsible for the PBA activity. Protein A failed to induce IgG synthesis in spleen cells from normal mice, even though it binds effectively to IgG molecules. Lymphocytes treated with anti-immunoglobulin antisera followed by protein A were not activated to a larger extent than non-pretreated cells, although only the former cells bound protein A. Finally, direct attempts to suppress the PBA property of protein A by blocking the Fc binding ability with serum or human gamma globulin failed. We concluded that protein A possesses two separate biological properties, namely to interact with the Fc receptor on Ig molecules and to act as a PBA, and these properties are carried out by different parts of the molecule. These findings confirm previous failures to find an active role of the Ig receptors on B lymphocytes in the triggering process.