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Published on: March 1, 2011
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.
Abstract:
In this report we have studied the functional effects of a wide range of interleukin 6 concentrations on human B cells. B cells purified from tonsils and from five of six spleens proliferated directly in a dose-dependent manner in the presence of low concentrations (1-100 pg/ml) of IL 6 whereas B cells from the sixth spleen proliferated only after in vitro anti-mu antibodies activation. Only large B cells (presumably in vivo activated B cells) were responsive to IL 6. High concentrations of IL 6 (1-10 ng/ml) did not trigger B cell proliferation but were able to up-regulate the expression of the B5 activation antigen on B cells, whereas the expression of two other B cell antigens (CD20 and CD23) was unchanged. At all concentrations of IL 6 tested (0.01-10 ng/ml) no B cell differentiation occurred after 7 days culture. Depletion before culture of B5+ cells from the B cell-enriched spleen cell preparation abolished both the proliferative effect and up-regulation of B5 antigen induced by IL 6, indicating that this lymphokine acted primarily on activated B cells. This differential effect of "low" and "high" concentrations of IL 6 on activated B cells may solve controversy on the role of IL 6 as an early or late agent in B cell maturation.

