Tespa1 Deficiency Dampens Thymus-Dependent B-Cell Activation and Attenuates Collagen-Induced Arthritis in Mice
Thymocyte-expressed, positive selection-associated 1 (Tespa1) plays an important role in both T cell receptor (TCR)-driven thymocyte development and in the FcεRI-mediated activation of mast cells. Herein, we show that lack of Tespa1 does not impair B cell development but dampens the in vitro activation and proliferation of B cells induced by T cell-dependent (TD) antigens, significantly reduces serum antibody concentrations in vivo, and impairs germinal center formation in both aged and TD antigen-immunized mice. We also provide evidence that dysregulated signaling in Tespa1-deficient B cells may be linked to CD40-induced TRAF6 degradation, and subsequent effects on 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-2 (PLCγ2) phosphorylation, MAPK activation, and calcium influx. Furthermore, we demonstrate that Tespa1 plays a critical role in pathogenic B cells, since Tespa1-deficient chimeric mice showed a lower incidence and clinical disease severity of collagen-induced arthritis. Overall, our study demonstrates that Tespa1 is essential for TD B cell responses, and suggests an important role for Tespa1 during the development of autoimmune arthritis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Frontiers in immunology - 9(2018) vom: 15., Seite 965 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yao, Yunliang [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.07.2019 Date Revised 03.07.2019 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2018.00965 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Thymocyte-expressed, positive selection-associated 1 (Tespa1) plays an important role in both T cell receptor (TCR)-driven thymocyte development and in the FcεRI-mediated activation of mast cells. Herein, we show that lack of Tespa1 does not impair B cell development but dampens the in vitro activation and proliferation of B cells induced by T cell-dependent (TD) antigens, significantly reduces serum antibody concentrations in vivo, and impairs germinal center formation in both aged and TD antigen-immunized mice. We also provide evidence that dysregulated signaling in Tespa1-deficient B cells may be linked to CD40-induced TRAF6 degradation, and subsequent effects on 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-2 (PLCγ2) phosphorylation, MAPK activation, and calcium influx. Furthermore, we demonstrate that Tespa1 plays a critical role in pathogenic B cells, since Tespa1-deficient chimeric mice showed a lower incidence and clinical disease severity of collagen-induced arthritis. Overall, our study demonstrates that Tespa1 is essential for TD B cell responses, and suggests an important role for Tespa1 during the development of autoimmune arthritis | ||
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| 700 | 1 | |a Qian, Jin |e verfasserin |4 aut | |
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| 700 | 1 | |a Sun, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a An, Xiangli |e verfasserin |4 aut | |
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| 700 | 1 | |a Zhao, Hongxing |e verfasserin |4 aut | |
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