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International Immunology, Vol. 11, No. 11, 1819-1828, November 1999
© 1999 Japanese Society for Immunology

Th2 cytokine dependence of IgD production by normal human B cells

Isabelle Levan-Petit, Eric Lelievre, Anne Barra, Anne Limosin, Bruno Gombert, Jean-Louis Preud'homme and Jean-Claude Lecron

ESA CNRS 6031, IBMIG, 40 Avenue du Recteur Pineau, 86022 Poitiers Cedex, France

Correspondence to: J.-C. Lecron

IgD is a minor component of serum Ig and the control of IgD secretion is virtually unknown. We measured concentrations of IgD (and IgE and IgM as controls) in culture supernatants of peripheral blood mononuclear cells (PBMC) from 60 normal donors as well as mononuclear cells from 10 tonsils following culture in the absence or presence of CD40 mAb and cytokines. Low levels of IgD were measured in cultures of PBMC, either unstimulated or stimulated by anti-CD40 antibodies. IL-4 and IL-10 significantly increased IgD production by CD40 mAb-stimulated cells in the majority of normal subjects studied, whereas in a limited number of individuals, spontaneous IgD production was either low or high, but with no increase upon stimulation. Spontaneous IgD production by tonsil-derived mononuclear cells was higher than by PBMC and 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 spontaneous as well as CD40- and cytokine-induced IgD production by PBMC, but not by tonsil mononuclear cells. Activation by IL-4 of CD40-stimulated purified B cells from tonsil and PBMC, and by IL-10 of tonsil B cells increased IgD production, whereas IL-2 and IFN-{gamma} had no detectable inhibitory effect. This suggests that accessory cells indirectly regulate IgD synthesis. IgD production induced in PBMC by IL-4 or IL-10 appeared to result from an active synthesis, and correlated with an increase in the number of IgD-containing plasma cells as demonstrated by immunofluorescence and increased expression of secreted IgD transcripts. These findings suggest that IgD production by normal peripheral blood human B cells is regulated positively by Th2 cytokines and negatively by Th1 cytokines.

Keywords: CD40, IgD, peripheral blood mononuclear cell, Th1, Th2, tonsil

Transmitting editor: J. Borst


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