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Published on: November 1, 2015
Role of IL-12 in human B lymphocyte proliferation and differentiation
1Department of Immunology, Mayo Clinic/Foundation, Rochester, MN 55905.
Insights
Interleukin-12 (IL-12) modestly enhances B cell growth but requires IL-2 to significantly boost Ig secretion. IL-12 acts as a potent costimulus for B cell differentiation, distinct from IL-2 signals.
Area of Science:
- Immunology
- Cell Biology
Background:
- Interleukin-12 (IL-12) is a cytokine with known immunomodulatory functions.
- Its specific role in human peripheral blood B cell responsiveness requires further elucidation.
Purpose of the Study:
- To investigate the direct effects of IL-12 on human B cell growth and differentiation.
- To determine if IL-12 can act as a B cell differentiation factor, alone or in combination with other cytokines.
Main Methods:
- FACS-purified human B cells were used (>99% purity).
- A polyclonal B cell activation system with Cowan I Staphylococcus aureus was employed.
- B cell growth, differentiation, and immunoglobulin (Ig) secretion were measured.
- Interferon-gamma (IFN-γ) levels and effects were assessed.
Main Results:
- IL-12 showed modest augmentation of B cell growth but was ineffective alone for differentiation.
- IL-12 significantly enhanced Ig secretion when combined with IL-2, acting as a potent costimulus.
- IL-12's effects on B cells were direct, not mediated by T cells, NK cells, or IFN-γ.
Conclusions:
- IL-12 is a potent costimulus for B cell differentiation, particularly enhancing IL-2-driven Ig secretion.
- The signaling pathways of IL-12 in B cell differentiation appear distinct from those of IL-2.
Abstract:
The role of IL-12 in human peripheral blood B cell responsiveness was examined. To analyze the ability of IL-12 to directly mediate B cell growth and/or differentiation, FACS-purified (> 99% pure) B cells were studied and a polyclonal B cell-activating system utilizing Cowan I Staphylococcus aureus was used. Whereas IL-2 is highly effective in this system in promoting both B cell growth and differentiation, IL-12 was observed only to augment modestly B cell growth and to be ineffective by itself as a B cell differentiation factor for S. aureus-stimulated B cells. However, IL-12 markedly enhanced Ig secretion when added in the presence of IL-2. Moreover, when the ability of IL-12 to augment IL-2-dependent B cell Ig secretion was compared with the ability of several known auxiliary B cell differentiation factors, IL-12 was observed to be the most potent cytokine that could costimulate with IL-2. Analysis of IL-12-stimulated B cell cultures failed to reveal outgrowth of T cells and NK cells. In addition, assessment of IFN-gamma levels in IL-12-driven B cell culture supernatants and analysis of IFN-gamma effects on B cell responses added additional support to the conclusion that IL-12 directly modulates B cell function. Finally, these results suggest that IL-12 is a potent constimulus of B cell differentiation and that the signals conveyed by IL-12 seem to be qualitatively distinct from the differentiative signals delivered by other cytokines such as IL-2.
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