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.

• Publication year

  1993

• Venue

  Journal of Immunology

• Publication date

  1993-12-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.4049/jimmunol.151.11.6525PMID 8245483
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Fresh SLE B cells secreted high levels of IL-6 without in vitro stimulation, supporting an autocrine IL-6/IL-6 receptor activation pathway in these cells.

  Confidence 0.97

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewGahyoun (29ua5897xm) review
• Anti-IL-6 receptor antibody and anti-Tac antibody strongly inhibited spontaneous autoantibody production by SLE B cells.

  Confidence 0.96

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewGahyoun (29ua5897xm) review
• Fresh blood B cells from most patients with SLE constitutively expressed IL-6 receptor and IL-2 receptor without in vitro stimulation.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewGahyoun (29ua5897xm) review

• anti-il-6 receptor antibody

  antibody

  An antibody used to block IL-6 binding to its receptor in the B-cell cultures.

  Aliases: anti-IL-6R antibody

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewGahyoun (29ua5897xm) review
• anti-tac antibody

  antibody

  An antibody against the Tac/IL-2 receptor used to block IL-2 receptor signaling in culture.

  Aliases: Tac, anti-Tac

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewGahyoun (29ua5897xm) review
• autoantibody production

  process

  Production of self-reactive antibodies by cultured B cells, including the spontaneous output measured in this assay.

  Aliases: autoantibody secretion

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewGahyoun (29ua5897xm) review
• autocrine il-6/il-6 receptor activation

  signaling pathway

  A self-stimulatory signaling loop in which B-cell-derived IL-6 acts back on IL-6 receptors on the same cells.

  Aliases: IL-6/IL-6R autocrine loop

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewGahyoun (29ua5897xm) review
• il-2 receptor

  receptor

  A receptor on B cells that binds IL-2 and is compared here with IL-6 receptor expression on SLE B cells.

  Aliases: IL-2R

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewGahyoun (29ua5897xm) review
• il-6

  cytokine

  A cytokine secreted by B cells and measured in fresh SLE B-cell supernatants.

  Aliases: interleukin-6

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewGahyoun (29ua5897xm) review
• il-6 receptor

  receptor

  A receptor on B cells that binds IL-6 and is assessed here for constitutive expression in SLE blood B cells.

  Aliases: IL-6R

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewGahyoun (29ua5897xm) review
• sle b cells

  cell type

  Peripheral blood B cells isolated from patients with systemic lupus erythematosus.

  Aliases: lupus B cells

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewKiller Whale (322360f1c1) reviewGahyoun (29ua5897xm) review

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