Protein A of Staphylococcus aureus is mitogenic for IgG-bearing, but also for a subpopulation of IgM- and/or IgD-bearing human lymphocytes.

The nature of lymphocyte subsets activated by soluble and insoluble protein A (SpA) was investigated by testing the ability of human tonsil populations to form rosettes with human red blood cells coated with SpA (SpA-HRBC) and to respond to SpA, SpA coupled to Sepharose beads (SpA-Seph) and strain Cowan I (StaCw). Purified human T cells, which were unable to form rosettes with SpA-HRBC, were not activated by SpA-Seph or StaCw, whereas B-cell enriched suspensions, where the number of lymphocytes forming rosettes with SpA-HRBC was significantly increased in comparison with that found in unfractionated populations, showed DNA synthesis equal to or greater than unseparated lymphocytes. In contrast, soluble SpA was unable to activate highly purified B lymphocytes in 3 day cultures and induced higher DNA synthesis in unseparated than in purified human T cells. Tonsil cell suspensions depleted in cells forming rosettes with SpA-HRBC synthesized significantly less DNA in the presence of SpA-Seph and lost the ability to respond to StaCw. The depletion in either IgG-bearing or IgM- and/or IgD-bearing cells induced a reduction in the response of lymphocytes to SpA-Seph and StaCw. Depletion in IgM- and/or IgD-bearing cells induced a more marked decrease in the response to StaCw than depletion in IgG-bearing lymphocytes, while the decrease of the response to SpA-Seph, induced by depletion in IgM- and/or IgD-bearing cells, was lower than that induced by depletion in IgG-bearing lymphocytes. In contrast, soluble SpA-induced proliferation was not significantly affected by depletion of cells forming rosettes with SpA-HRBC or of IgG-bearing or IgM- and/or IgD-bearing lymphocytes. These results suggest that the mitogenicity of SpA-Seph and StaCw is due to a selective binding of insoluble SpA to components present on the membrane of either IgG-bearing or IgM- and/or IgD-bearing lymphocytes. They also indicate that the potentiation of T-cell response to soluble SpA, induced by the presence in culture of non-T cells, is not due to B lymphocytes which are able to form rosettes with SpA-HRBC and to respond to SpA itself when it is presented to the cells on an insoluble matrix.