T(h)2 cytokine dependence of IgD production by normal human B cells

IgD is a minor component of serum Ig and the control of IgD secretion is vi rtually unknown. We measured concentrations of IgD (and IgE and IgM as cont rols) in culture supernatants of peripheral blood mononuclear cells (PBMC) from 60 normal donors as well as mononuclear cells from 10 tonsils followin g culture in the absence or presence of CD40 mAb and cytokines, Low revels of IgD were measured in cultures of PBMC, either unstimulated or stimulated by anti-CD40 antibodies. IL-4 and IL-10 significantly increased IgD produc tion by CD40 mAb-stimulated cells in the majority of normal subjects studie d, whereas in a limited number of individuals, spontaneous IgD production w as either low or high, but with no increase upon stimulation. Spontaneous I gD production by tonsil-derived mononuclear cells was higher than by PBMC a nd increased after CD40 stimulation and even more in the presence of IL-10, but not IL-4, IL-2 and IFN-gamma exerted a dose-dependent inhibition on sp ontaneous as well as CD40- and cytokine-induced IgD production by PBMC, but not by tonsil mononuclear cells. Activation by IL-4 of CD40-stimulated pur ified a cells from tonsil and PBMC, and by IL-10 of tonsil B cells increase d IgD production, whereas IL-2 and IFN-gamma had no detectable inhibitory e ffect, This Suggests that accessory cells indirectly regulate IgD synthesis . IgD production induced in PBMC by IL-4 or IL-10 appeared to result from a n active synthesis, and correlated with an increase in the number of IgD-co ntaining plasma cells as demonstrated by immunofluorescence and increased e xpression of Secreted IgD transcripts. These findings suggest that Ion prod uction by normal peripheral brood human a cells is regulated positively by T(h)2 cytokines and negatively by T(h)1 cytokines.