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Published on: September 27, 2013
Regulation of B lymphocyte responses to IL-4 and IFN-gamma by activation through Ly-6A/E molecules
1Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.
Insights
Ly-6A/E proteins regulate B cell responses. This study demonstrates their direct impact on B cell proliferation and activation, suggesting a key role in immune modulation.
Area of Science:
- Immunology
- Cell Biology
Background:
- The Ly-6 family of cell surface molecules is known to be involved in T cell activation.
- The specific role of Ly-6A/E proteins in B lymphocyte function remains largely unexplored.
Purpose of the Study:
- To investigate the functional role of Ly-6A/E proteins in normal B lymphocyte responses.
- To determine if Ly-6A/E proteins modulate B cell proliferation and activation.
Main Methods:
- In vitro culture of B cells with cytokines (IFN-gamma, IL-4) and anti-Ly-6A/E monoclonal antibody (mAb).
- Assays to measure B cell proliferation and surface antigen expression.
- Co-culture experiments with T and B cells, and analysis of B cell lymphoma cell lines.
Main Results:
- Anti-Ly-6A/E mAb induced proliferation in resting B cells cultured with IFN-gamma and IL-4.
- The anti-Ly-6A/E mAb restored proliferation inhibited by anti-IgM.
- Ly-6A/E surface expression was upregulated by anti-Ly-6A/E in an IFN-gamma-dependent manner.
- T cells did not significantly contribute to the observed B cell proliferation.
Conclusions:
- Ly-6A/E proteins are functional on B lymphocytes.
- These proteins appear to directly modulate B cell activation and proliferation.
- Ly-6A/E may play a regulatory role in the immune response mediated by B cells.
Abstract:
The Ly-6 family of cell surface molecules has previously been shown to participate in T cell activation. We show that Ly-6A/E proteins also modulated the response of normal B lymphocytes in three separate in vitro assays. First, unfractionated or small resting B cells proliferated when cultured with IFN-gamma, IL-4, and an anti-Ly-6A/E mAb. Second, this anti-Ly-6A/E mAb restored B cell proliferation responses that were inhibited when coculturing the B cells in IFN-gamma, IL-4, and anti-IgM. Third, anti-Ly-6A/E specifically up-regulated the cell surface expression of its own Ag, and this response was dependent upon co-stimulation with IFN-gamma. Mixing of T and B cells in culture suggested that T cells did not contribute substantially to the B cell proliferative response. Moreover, up-regulation of Ly-6A/E was observed for one B cell lymphoma, WEHI-231. Therefore, it appeared that modulation of B cell function by anti-Ly-6A/E was due to a direct effect of the mAb binding to the B cells. Taken together, these data suggest Ly-6A/E proteins are functional on B cells and may play a regulatory role in B cell activation.
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