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Modulation of spontaneous B-cell differentiation in macroglobulinemia by retinoic acid

Y Levy, S Labaume, MC Gendron and JC Brouet

Laboratory of Immunopathology, Hopital Saint-Louis, Paris, France.

We previously showed that clonal blood B cells from patients with macroglobulinemia spontaneously differentiate in vitro to plasma cells. This process is dependent on an interleukin (IL)-6 autocrine pathway. We investigate here whether all-trans-retinoic acid (RA) interferes with B-cell differentiation either in patients with IgM gammapathy of undetermined significance (MGUS) or Waldenstrom's macroglobulinemia (WM). RA at a concentration of 10(-5) to 10(-8) mol/L inhibited by 50% to 80% the in vitro differentiation of purified B cells from four of five patients with MGUS and from one of five patients with WM as assessed by the IgM content of day 7 culture supernatants. We next determined whether this effect could be related to an inhibition of IL- 6 secretion by cultured B cells and/or a downregulation of the IL-6 receptor (IL-6R), which was constitutively expressed on patients' blood B cells. A 50% to 100% (mean, 80%) inhibition of IL-6 production was found in seven of 10 patients (five with MGUS and two with WM). The IL- 6R was no more detectable on cells from patients with MGUS after 2 days of treatment with RA and slightly downregulated in patients with WM. It was of interest that B cells susceptible to the action of RA belonged mostly to patients with IgM MGUS, which reinforces our previous data showing distinct requirements for IL-6-dependent differentiation of blood B cells from patients with VM or IgM MGUS.

Volume 83, Issue 8, pp. 2206-2210, 04/15/1994
Copyright © 1994 by The American Society of Hematology


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M. A. Dimopoulos, P. Panayiotidis, L. A. Moulopoulos, P. Sfikakis, and M. Dalakas
Waldenstrom’s Macroglobulinemia: Clinical Features, Complications, and Management
J. Clin. Oncol., January 5, 2000; 18(1): 214 - 214.
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