Activation of human B cells: involvement of surface immunoglobulin as evidenced by two biochemically distinct types...

If activation of human B cells by Staphylococcus aureus proceeds through interaction of surface immunoglobulin with Staphylococcal protein A, then immunoglobulins should be produced that are capable of binding to protein A as a consequence of such stimulation. In the present report it is shown that two biochemically distinct types of response to S. aureus are demonstrable in human peripheral blood lymphocytes. Two types of IgM are produced: IgM capable of binding to protein A, and IgM that does not bind and can be recovered by immunoprecipitation with anti-Ig antibodies. Cloned cell lines produce one of either type of Ig, but not both. Therefore, interaction of protein A with Ig alone cannot account for the stimulatory properties of S. aureus. When S. aureus is used in conjunction with pokeweek mitogen, a synergistic effect between the two mitogens is seen. Under conditions of optimal synergistic stimulation, the increase in immunoglobulin production is seen virtually exclusively in the category of molecules capable of binding to protein A. These results offer strong support for a model where optimal differentiation of human B cells to plasma cells is contingent upon receiving at least two signals: one signal is delivered to the surface immunoglobulin, and one signal delivered to the B cell in a T cell and/or monocyte dependent fashion (B cell growth and differentiation factors).