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Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3605-3615
Modulation and Functional Involvement of CB2 Peripheral Cannabinoid
Receptors During B-Cell Differentiation
Pierre Carayon,
Jean Marchand,
Danielle Dussossoy,
Jean-Marie Derocq,
Omar Jbilo,
Annie Bord,
Monsif Bouaboula,
Sylvaine Galiègue,
Paul Mondière,
Géraldine Pénarier,
Gérard Le Fur,
Thierry Defrance, and
Pierre Casellas
From the Immunology Department, Sanofi Recherche, Montpellier,
France; and the Immunité et vaccination, INSERM U404, Institut
Pasteur de Lyon, Lyon, France.
Two subtypes of G-protein-coupled cannabinoid receptors have been
identified to date: the CB1 central receptor subtype, which is mainly
expressed in the brain, and the CB2 peripheral receptor subtype, which
appears particularly abundant in the immune system. We investigated the
expression of CB2 receptors in leukocytes using anti-CB2 receptor
immunopurified polyclonal antibodies. We showed that peripheral blood
and tonsillar B cells were the leukocyte subsets expressing the highest
amount of CB2 receptor proteins. Dual-color confocal microscopy
performed on tonsillar tissues showed a marked expression of CB2
receptors in mantle zones of secondary follicles, whereas germinal
centers (GC) were weakly stained, suggesting a modulation of this
receptor during the differentiation stages from virgin B lymphocytes to
memory B cells. Indeed, we showed a clear downregulation of CB2
receptor expression during B-cell differentiation both at transcript
and protein levels. The lowest expression was observed in GC
proliferating centroblasts. Furthermore, we investigated the effect of
the cannabinoid agonist CP55,940 on the CD40-mediated proliferation of
both virgin and GC B-cell subsets. We found that CP55,940 enhanced the
proliferation of both subsets and that this enhancement was blocked by
the CB2 receptor antagonist SR 144528 but not by the CB1 receptor
antagonist SR 141716. Finally, we observed that CB2 receptors were
dramatically upregulated in both B-cell subsets during the first 24 hours of CD40-mediated activation. These data strongly support an
involvement of CB2 receptors during B-cell differentiation.
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