Lymphocyte function in human bone marrow. III. Isotype commitment, metabolic and secretory characteristics of...

We have examined the functional and metabolic properties of immunoglobulin (Ig)-secreting cells in adult (rib) bone marrow, the tissue which provides the major proportion of serum Igs. In the absence of polyclonal activators, high rate Ig production (1-2 micrograms/day/10(6) marrow mononuclear cells) was sustained from the beginning of culture throughout 2 weeks and then declined. Ten percent of the Ig secreted was of the IgM isotype and IgG/A made up the remainder at equal proportions. Infection of marrow cells with Epstein-Barr virus (EBV) induced the production of large amounts of IgM, but virtually all IgG/A-committed cells were refractory to stimulation with EBV. Both EBV-induced and the "spontaneous" Ig production was inhibited by cycloheximide, but only EBV-induced IgM production was blocked by hydroxyurea and gamma-irradiation. The polyclonal activators PHA and PWM induce suppressor-T-cell activity in marrow cultures. This suppressor function involves nonproliferating cells which acquire suppressive activity 3-4 days after mitogenic activation. Prednisolone and cyclosporine A modulate Ig production in cultures of peripheral lymphocytes but had no effect on Ig secretion in marrow cell cultures. This observation was reminiscent of the absent or at best marginal short-term effects on in vivo serum Ig levels which is typical for these drugs. Our observations suggest that the marrow Ig-producing B-lymphoid cell compartment shows major differences to other tissue sites with respect to properties of the Ig-secreting cells the immunoregulatory activities able to control their function, and the response of these cells to clinically important drugs.