Surface immunoglobulins are involved in the interaction of protein A with human B cells and in the triggering of B cell proliferation induced by protein A-containing Staphylococcus aureus.

The nature of surface components responsible for the reactivity of a subset of human B cells with staphylococcal protein A (SpA) was studied. The ability of normal non-T cells or non-T cells from patients with chronic lymphocytic leukemia (CLL) to form rosettes with human red blood cells coated with SpA (SpA-HRBC) was strongly inhibited or abolished by incubation with F(ab')2 fragments of antibodies against human immunoglobulin (Ig), whereas the incubation with F(ab')2 fragments of antibodies against a non-Ig cell surface antigen, such as beta 2-microglobulin, had no effect on the SpA-rosetting of human lymphocytes. The role of the reaction between surface Ig (sIg) and SpA in the triggering of the proliferative response induced by Staphylococcus aureus bacteria strain Cowan I (Cowan Staph) on normal or leukemic non-T cells was also investigated. A parallelism was observed between the mitogenic activity on normal human non-T cells of Cowan Staph and F(ab')2 fragments of immunosorbent-purified rabbit antibodies to human mu-chain. On the other hand, monovalent Fab fragments of anti-F(ab')2 or anti-mu chain antibodies were unable to activate human non-T lymphocytes, but usually induced a partial inhibition of the Cowan Staph-induced cell proliferation. Non-T cells from 2 patients with CLL did not respond to either Fab or F(ab')2 fragments of anti-Ig antibodies, but were stimulated to proliferate by Cowan Staph. However, the proliferative response of non-T cells from these patients to Cowan Staph was markedly inhibited or abolished by the addition to the cultures of F(ab')2 fragments of anti-Ig antibodies. Antibody preparations to human F(ab')2 or gamma-chain inhibited the response of IgG-bearing leukemic cells, whereas the Cowan Staph-induced proliferation of IgM-bearing leukemic lymphocytes was inhibited by the addition to the cultures of either anti-F(ab')2 or anti-mu chain antibodies. The proliferative response to Cowan Staph or normal non-T cells was also inhibited by the addition to the cultures of human and guinea pig polyclonal IgG, whereas IgG from other species, such as goat, ox, horse, and rabbit, were poorly or not at all inhibitory. On a molar basis, the F(ab')2 preparation from human IgG was as potent an inhibitor as intact IgG molecules, whereas Fc gamma was much less effective in inhibiting the Cowan Staph-induced cell proliferation. A monoclonal IgM, isolated from the serum of a patient with CLL, whose lymphocytes were able to form rosettes with SpA-HRBC and to proliferate in vitro after stimulation with Cowan Staph, also showed a marked inhibitory activity on the Cowan Staph-induced proliferation or normal non-T cells. These data suggest that an interaction between SpA present on the bacterial cell wall and a structure located in the Fab region of sIg, which is shared by sIgM, sIgG, and perhaps also by sIg of other classes, plays an important role in the triggering of B cell proliferation induced by SpA-containing staphylococci.