Staphylococcal protein A, a T cell-regulated polyclonal activator of human B cells
Lipsky, P.E.
Journal of Immunology 125(1): 155-162
1980
ISSN/ISBN: 0022-1767 PMID: 6966649 Document Number: 158292
The capacity of staphylococcal protein A (SPA) to trigger the generation of immunoglobulin [Ig]-secreting cells (ISC) from human peripheral blood mononuclear cells (PBM) was examined. SPA at low concentrations (.ltoreq. 1 .mu.g/ml) induced polyclonal activation of human peripheral blood B [bone marrow-derived] cells, whereas higher concentrations (.gtoreq. 5 .mu.g/ml) tended to suppress the response. SPA triggered the differentiation of IgM- and IgG-secreting cells. Although the magnitude of theIgM response was comparable to that stimulated by pokeweed mitogen (PWM), SPA led to the differentiation of many fewer IgG-secreting cells than PWM. The response to SPA was absolutely T [thymus-derived] cell dependent. The response was regulated by suppressor T cells. Inhibition of responsiveness observed with higher concentrations of SPA could be ascribed to the activity of suppressor T cells. PBM from normal individuals who responded poorly to lower concentrations of SPA had expanded suppressor cell activity. T cell suppression could be abolished by inhibiting T cell DNA synthesis with mitomycin C. SPA-triggered suppressor T cells were not specific in their action, since they could suppress PWM-induced generation of ISC. In a number of individuals, suppressor T cells appeared to have different dose-response characteristics than helper T cells; they required higher concentrations of SPA to be activated. The ratio of SPA-resonsive suppressor and helper T cells in PBM appeared quite low such that supplementation of B cell cultures with small numbers of T cells led to the expression of only help and little suppression. Although cell division was not necessary, SPA-induced helper T cell activity was augmented when the T cells were allowed to proliferate. SPA is a T cell-regulated activator of human peripheral blood B cells. Use of this probe should provide additional insights into the cellular interactions involved in the differentiation of antibody-forming cells in humans.