Constitutive expression of IL-6 receptors and their role in the excessive B cell function in patients with systemic lupus erythematosus.
Excessive B cell function including autoantibody production is a common feature of SLE and considered to be intimately associated with spontaneous lymphokine secretion by themselves. To clarify roles of IL-6/IL-6 receptor autocrine activation pathway in autoantibody production observed in patients with SLE, we studied expression and function of IL-6 receptors in comparison with those of IL-2 receptors, Tac on SLE B cells. IL-6 receptors and IL-2 receptors have been detected on B cells in the blood without any in vitro stimuli in most patients with SLE. The introduction of anti-IL-6 receptor antibody, which inhibits binding to the receptors of IL-6, and anti-IL-2 receptor antibody, anti-Tac to the cultures of SLE B cells resulted in potent inhibition of spontaneous production of polyclonal Ig and anti-DNA autoantibodies. In addition, fresh SLE B cells secreted high levels of IL-6 without any in vitro stimuli. These results indicate that constitutive expression of IL-6 receptors on B cells in conjunction with spontaneous IL-6 production by B cells induces autocrine B cell activation, which may lead to B cell hyperactivity and autoantibody secretion in SLE patients. Dysregulation of B cell activity observed in patients with SLE could thus be, at least in part, independent of T cell help.
Nagafuchi
H
H
Division of Allergy and Rheumatic Diseases, St. Marianna University School of Medicine, Kanagawa, Japan.
Suzuki
N
N
Mizushima
Y
Y
Sakane
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D002648:Child; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000032:analysis* / Q000502:physiology; D019947:Receptors, Interleukin-6
D000974:Antibodies, Antinuclear; D007376:Interleukin-2; D015850:Interleukin-6; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6