PRODUCTION OF IMMUNOGLOBULINS BY HUMAN SIGD(-) HUMAN BLOOD B-LYMPHOCYTES IN RESPONSE TO STIMULATION WITH ACTIVATED T-CELLS AND AGONISTIC ANTIBODIES - EFFECT OF IL-10, IL-2 AND MODE OF ACTIVATION OF T-CELLS() AND SIGD()

Production of IgM, IgG and IgA was induced from human blood B lymphocy tes by culturing with a CD40 MoAb and IL-2 for 9 days. Replacement of IL-2 by IL-10 markedly enhanced production of all three isotypes. High levels of immunoglobulin production also occurred when activated irra diated autologous T cells replaced the CD40 MoAb, and when IL-10 repla ced IL-2 in these cultures a spectacular increase in IgG production oc curred. The effectiveness of the T cell stimulus depended on the mode of purification of the T cells and the nature of the stimulant used to activate them. Differences in the kinetics and level of expression of CD40L on the various T cell preparations were observed, but did not a ccount for variations in immunoglobulin-inducing efficiency. Immunoglo bulin production from sIgD(+) and sIgD(-) B cells was investigated. Ig G and IgA were found in sIgD(+) cultures, indicating that some isotype switching had occurred, but the major part of the IgG and IgA secrete d was from cells already committed to these isotypes. Anti-IgD or anti -IgM MoAbs enhanced the proliferation of B cells induced by anti-CD40 antibody, but immunoglobulin production was not enhanced. Factors affe cting the balance of proliferation and differentiation are discussed.