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

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 differentiat...

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Bibliographic Details
Published in:Blood 1994-04, Vol.83 (8), p.2206-2210
Main Authors: LEVY, Y, LABAUME, S, GENDRON, M.-C, BROUET, J.-C
Format: Article
Language:English
Subjects:
B-Lymphocytes - drug effects
B-Lymphocytes - physiology
Biological and medical sciences
Cell Differentiation - drug effects
Cells, Cultured
Humans
Immunodeficiencies. Immunoglobulinopathies
Immunoglobulinopathies
Immunopathology
Interleukin-6 - metabolism
Medical sciences
Receptors, Interleukin - analysis
Receptors, Interleukin-6
Tretinoin - pharmacology
Waldenstrom Macroglobulinemia - blood
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Summary: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 Waldenström'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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V83.8.2206.2206