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B cells participate in thymic negative selection of murine auto-reactive CD4+ T cells.

Frommer F, Waisman A - PLoS ONE (2010)

Bottom Line: It is well documented that thymic epithelial cells participate in the process of negative selection in the thymus.Using a unique mouse model we show that B cells induce negative selection of self-reactive thymocytes in a process that leads to the deletion of these cells whereas regulatory T cells are spared.These findings have direct implication in autoimmunity, as expression of a myelin antigen by B cells in the thymus renders the mice resistant to autoimmune inflammation of the CNS.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.

ABSTRACT
It is well documented that thymic epithelial cells participate in the process of negative selection in the thymus. In recent years it was reported that also dendritic cells enter the thymus and contribute to this process, thus allowing for the depletion of thymocytes that are specific to peripherally expressed self-antigens. Here we report that also B cells may take part in the elimination of auto-reactive thymocytes. Using a unique mouse model we show that B cells induce negative selection of self-reactive thymocytes in a process that leads to the deletion of these cells whereas regulatory T cells are spared. These findings have direct implication in autoimmunity, as expression of a myelin antigen by B cells in the thymus renders the mice resistant to autoimmune inflammation of the CNS.

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Residual MOG-specific T cells in BMOG/2D2 mice downregulate Vβ11.LN of WT 2D2 and BMOG/2D2 mice were analyzed by FACS analysis for presence of CD4, Vα3.2 and Vβ11. Cells were analyzed for expression of Vα3.2 vs CD4 (dot blots). Cells were then gated on CD4+ Vα3.2+ T cells and the percentage of Vβ11-expressing cells among this population is shown by histogram overlay. The red line in the histograms refers to the red gate of CD4+ Va3.2+ cells in 2D2 mice, the blue line refers to CD4+ Va3.2+ cells (blue gate) of BMOG/2D2 mice. Colored numbers above the marker line indicate MFI (mean fluorescence intensity) of anti-Vβ11-PE for the respective populations.
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pone-0015372-g003: Residual MOG-specific T cells in BMOG/2D2 mice downregulate Vβ11.LN of WT 2D2 and BMOG/2D2 mice were analyzed by FACS analysis for presence of CD4, Vα3.2 and Vβ11. Cells were analyzed for expression of Vα3.2 vs CD4 (dot blots). Cells were then gated on CD4+ Vα3.2+ T cells and the percentage of Vβ11-expressing cells among this population is shown by histogram overlay. The red line in the histograms refers to the red gate of CD4+ Va3.2+ cells in 2D2 mice, the blue line refers to CD4+ Va3.2+ cells (blue gate) of BMOG/2D2 mice. Colored numbers above the marker line indicate MFI (mean fluorescence intensity) of anti-Vβ11-PE for the respective populations.

Mentions: The number of CD4+Vα3.2+ T cells is dramatically reduced in the LN of BMOG/2D2 compared to 2D2 mice (Fig. 1 and 3). Interestingly, all surviving cells additionally still express the transgenic TCR β chain, namely Vβ11 (Fig. 3). But the expression levels of the TCR Vβ11 are reduced in mice where B cells present the MOG peptide (see histogram in Fig. 3). These findings suggest that the remaining transgenic TCR-expressing T cells can recognize the MOG peptide presented by B cells in the periphery, as reduced TCR expression is an indicative of recent T cell activation.


B cells participate in thymic negative selection of murine auto-reactive CD4+ T cells.

Frommer F, Waisman A - PLoS ONE (2010)

Residual MOG-specific T cells in BMOG/2D2 mice downregulate Vβ11.LN of WT 2D2 and BMOG/2D2 mice were analyzed by FACS analysis for presence of CD4, Vα3.2 and Vβ11. Cells were analyzed for expression of Vα3.2 vs CD4 (dot blots). Cells were then gated on CD4+ Vα3.2+ T cells and the percentage of Vβ11-expressing cells among this population is shown by histogram overlay. The red line in the histograms refers to the red gate of CD4+ Va3.2+ cells in 2D2 mice, the blue line refers to CD4+ Va3.2+ cells (blue gate) of BMOG/2D2 mice. Colored numbers above the marker line indicate MFI (mean fluorescence intensity) of anti-Vβ11-PE for the respective populations.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2958132&req=5

pone-0015372-g003: Residual MOG-specific T cells in BMOG/2D2 mice downregulate Vβ11.LN of WT 2D2 and BMOG/2D2 mice were analyzed by FACS analysis for presence of CD4, Vα3.2 and Vβ11. Cells were analyzed for expression of Vα3.2 vs CD4 (dot blots). Cells were then gated on CD4+ Vα3.2+ T cells and the percentage of Vβ11-expressing cells among this population is shown by histogram overlay. The red line in the histograms refers to the red gate of CD4+ Va3.2+ cells in 2D2 mice, the blue line refers to CD4+ Va3.2+ cells (blue gate) of BMOG/2D2 mice. Colored numbers above the marker line indicate MFI (mean fluorescence intensity) of anti-Vβ11-PE for the respective populations.
Mentions: The number of CD4+Vα3.2+ T cells is dramatically reduced in the LN of BMOG/2D2 compared to 2D2 mice (Fig. 1 and 3). Interestingly, all surviving cells additionally still express the transgenic TCR β chain, namely Vβ11 (Fig. 3). But the expression levels of the TCR Vβ11 are reduced in mice where B cells present the MOG peptide (see histogram in Fig. 3). These findings suggest that the remaining transgenic TCR-expressing T cells can recognize the MOG peptide presented by B cells in the periphery, as reduced TCR expression is an indicative of recent T cell activation.

Bottom Line: It is well documented that thymic epithelial cells participate in the process of negative selection in the thymus.Using a unique mouse model we show that B cells induce negative selection of self-reactive thymocytes in a process that leads to the deletion of these cells whereas regulatory T cells are spared.These findings have direct implication in autoimmunity, as expression of a myelin antigen by B cells in the thymus renders the mice resistant to autoimmune inflammation of the CNS.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.

ABSTRACT
It is well documented that thymic epithelial cells participate in the process of negative selection in the thymus. In recent years it was reported that also dendritic cells enter the thymus and contribute to this process, thus allowing for the depletion of thymocytes that are specific to peripherally expressed self-antigens. Here we report that also B cells may take part in the elimination of auto-reactive thymocytes. Using a unique mouse model we show that B cells induce negative selection of self-reactive thymocytes in a process that leads to the deletion of these cells whereas regulatory T cells are spared. These findings have direct implication in autoimmunity, as expression of a myelin antigen by B cells in the thymus renders the mice resistant to autoimmune inflammation of the CNS.

Show MeSH
Related in: MedlinePlus