Decreased catecholamine-induced cell death in B lymphocytes from patients with rheumatoid arthritis

The expression of beta(2)-adrenergic receptors (beta(2)-R) on B lymphocytes and agonist-induced cAMP production is reduced in patients with rheumatoid arthritis (RA). To further study functional consequences of the diminished beta(2)(-)R density on B lymphocytes in RA patients, agonist-induced cell death was evaluated and compared to healthy controls. B lymphocytes from patients with RA and healthy controls were activated with anti-IgM-antibody. Coincubation was carried out with isoprenaline (iso, 0.001-10 muM). Apoptotic and necrotic cells were determined using Annexin-V and propidium-iodide staining. beta(2)-R-induced cell death in B cells from healthy volunteers was stimulated after 24 h (medium, 21.2 +/- 1.6%; iso, 34.6 +/- 4.4%; increase 59.3 +/- 10.1%). However, in RA patients the increase in cell death following beta(2)-R stimulation (21.8 +/- 8.9%) was significantly impaired (p = 0.02). Our data demonstrate that catecholamine-induced cell death after stimulation of beta(2)-R on B lymphocytes is decreased in RA patients, possibly contributing to the pathogenesis of the disease.