T-cell regulation of immunoglobulin synthesis and proliferation in pokeweed (Pa-1)-stimulated human lymphocyte cultures

Abstract

In pokeweed (Pa-1)-stimulated human lymphocyte cultures, T cells are essential for the survival, proliferation, plasma-cell development, and high-rate Ig secretion of B cells. Their effects are T-cell-specific in the sense that B-cell stimulation does not take place in the absence of T cells even when fibroblasts or monocytes are provided. The experimental system is the most effective model for activation of human B lymphocytes so far described. Plasmablast development requires approximately 7 days in culture. In T + B-cell cultures established at 1 X 10(6)/ml (1 X 10(4)/mm2) initial cell density, plasma cells can secrete, on the average, as much as 40-70 pg IgM or IgG per cell per day. When the initial T-cell density is increased well above 1.0 X 10(6)/ml, a T-cell-mediated depression of Ig synthesis becomes predominant. Thus, in the pokeweed model T-cell effects represent a balance of helper and suppressor influences. The study also shows that B cells are heterogeneous. A non-adherent IgG-committed (smIg-?) TONSIL B-cell population seems to be less susceptible to T suppressor effects than normal tonsil B cells. This subset proliferates particularly well and synthesizes large quantities of IgG in the presence of large initial proportions of T cells.