IgG aggregates of different sizes stimulate or suppress Ig secretion by human lymphocytes in vitro.

The regulatory effects of IgG aggregates on Ig production in vitro by human peripheral blood lymphocytes were shown to be highly dependent on the aggregate size and the degree of mitogenic stimulation. Covalently linked oligometers of IgG were prepared with dimethylsuberimidate cross-linking and chromatographic separation; larger aggregates were prepared by heating (63 degrees C) and preparative zonal ultracentrifugation. The storage and culture conditions used were shown to preserve the stability of aggregate sizes. Although both positive and negative regulatory effects were seen with cells isolated directly from blood, more predictable dose-related effects were seen if cells were vigorously washed, possibly due to the removal of IgG or natural immune complexes bound by the cells in vivo. Some preparations of small IgG oligomers produced marked stimulation of Ig production, especially in cells cultured without mitogen or with suboptimal pokeweed mitogen doses. Aggregates containing six or more IgGs suppressed Ig production, especially when cells were stimulated by mitogen at optimal concentrations.