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Blood, Vol. 92 No. 5 (September 1), 1998:
pp. 1713-1720
Retinoic Acid Inhibits CD40 + Interleukin-4-Mediated IgE
Production In Vitro
M. Worm,
J.M. Krah,
R.A. Manz, and
B.M. Henz
From the Department of Dermatology, Charité-Virchow Klinikum,
Humboldt Universität and Deutsches Rheuma-Forschungszentrum,
Berlin, Germany.
To elucidate the role of retinoic acid (RA) in anti-CD40 + interleukin-4 (IL-4)-mediated B-cell activation, the effect of 10 12 to 106 mol/L RA was studied in
anti-CD40 (1 µg/mL) + IL-4 (5 ng/mL)-mediated proliferation and Ig
synthesis by human peripheral blood mononuclear cells (PBMC) and B
cells in healthy donors. Anti-CD40 + IL-4-mediated proliferation of
PBMC and B cells was inhibited by RA in a dose-dependent manner, with
maximal inhibition of 62% ± 5% in PBMC and 55% ± 4.4% in B
cells by all-trans RA, and 58% ± 6.7% and 51% ± 4.7%, respectively by 13-cis RA. IgE synthesis was even more markedly inhibited by RA starting at concentrations of >1014
mol/L for B cells and >1010 mol/L for PBMC. Maximal
inhibition of IgE production for B cells was at 108
mol/L for all-trans RA (94% ± 1.8%) and 96% ± 3.2% for
13-cis RA. Low concentrations of RA inhibiting IgE synthesis
(1010 mol/L) affected neither B-cell proliferation nor
the production of IgA, IgG, and IgM. Elucidation of the mechanism
involved in this inhibition of IgE production shows that epsilon
germline transcription is decreased by RA, whereas production of
interferon- (IFN-) was not enhanced in the presence
of RA. To differentiate whether the RA effect was mediated by RA
receptors  ,  , and , the expression of the retinoic acid
receptors (RAR) was examined by reverse transcriptase-polymerase chain
reaction (RT-PCR). The data show that unstimulated human peripheral B
cells express mRNA of the RA receptor , , and . Using
retinoids with different receptor binding specificity (CD336, CD437,
CD2019, CD367), dose-dependent inhibition of IgE synthesis was shown by
all four derivates, but was most marked by an RA binding the
receptor with high specificity. Taken together, this study shows that
RA inhibits IgE production of anti-CD40 + IL-4-stimulated B cells in
vitro.
© 1998 by The American Society of Hematology.
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