Differential effects of low and high concentrations of interleukin 6 on human B cells

Y Levy1, J P Fermand, J C Brouet

  • 1Laboratory of Immunochemistry and Immunopathology, INSERM U 108, Hôpital Saint-Louis, Paris, France.

Insights

Interleukin 6 (IL-6) at low concentrations promotes proliferation in activated human B cells. High IL-6 concentrations up-regulate B5 antigen expression, suggesting distinct roles in B cell activation and maturation.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Interleukin 6 (IL-6) is a pleiotropic cytokine with diverse roles in immune responses.
  • The specific effects of IL-6 on human B cell function, particularly at varying concentrations, remain incompletely understood.
  • Previous studies have yielded conflicting results regarding IL-6's role in B cell maturation.

Purpose of the Study:

  • To investigate the functional effects of a wide range of interleukin 6 (IL-6) concentrations on human B cells.
  • To elucidate the differential impact of low and high IL-6 concentrations on B cell proliferation, activation antigen expression, and differentiation.
  • To clarify the role of IL-6 in B cell maturation by examining its effects on activated B cells.

Main Methods:

  • Purification of human B cells from tonsils and spleens.
  • Culture of B cells with varying concentrations of IL-6 (0.01-10 ng/ml).
  • Assessment of B cell proliferation, expression of B cell antigens (B5, CD20, CD23), and differentiation.
  • Functional assays involving depletion of B5+ cells from spleen cell preparations.

Main Results:

  • Low IL-6 concentrations (1-100 pg/ml) induced dose-dependent proliferation in B cells from tonsils and most spleens, primarily affecting large, presumably in vivo activated B cells.
  • High IL-6 concentrations (1-10 ng/ml) did not induce proliferation but upregulated B5 antigen expression on B cells, without affecting CD20 or CD23.
  • No B cell differentiation was observed at any tested IL-6 concentration after 7 days of culture.
  • Depletion of B5+ cells abrogated IL-6-induced proliferation and B5 upregulation, confirming IL-6's primary action on activated B cells.

Conclusions:

  • Interleukin 6 exhibits differential effects on human B cells based on concentration, acting as a proliferative stimulus at low levels and an inducer of B5 antigen expression at high levels.
  • These findings suggest that IL-6 primarily targets activated B cells, influencing their activation state rather than driving terminal differentiation.
  • The distinct concentration-dependent effects of IL-6 provide a potential resolution to the controversy surrounding its role as an early or late factor in B cell maturation.