Intravenous immunoglobulin induces a functional silencing program similar to anergy in human B cells
Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved..
BACKGROUND: Chronic inflammatory and autoimmune diseases are largely due to inappropriate response of hyperactive or autoreactive B cells. These autoreactive B cells can evade central tolerance checkpoints and migrate to the periphery, where they would be silenced by anergy. Such anergic cells are characterized by B-cell receptor (BCR) desensitization and altered downstream signaling.
OBJECTIVE: We sought to determine whether intravenous immunoglobulin (IVIg) induces a nonresponsive state of B cells and to address the similarities of this mechanism to those described in anergy.
METHODS: Human B cells were stimulated with anti-IgM antibody, and effects of IVIg on several parameters, such as calcium release, tyrosine phosphorylation, BCR aggregation, BCR internalization, or transcriptional activity, were studied by using flow cytometry, confocal microscopy, Western blotting, and a quantitative PCR array.
RESULTS: IVIg-treated B cells show defects in activating coreceptor expression, calcium signaling, and BCR aggregation on engagement by antigen. IVIg also induces suppression of phosphoinositide 3-kinase signaling, which plays a central role in determining B-cell fate. All these events ultimately lead to profound modifications in gene expression, resulting in long-term functional but reversible silencing of IVIg-treated B cells.
CONCLUSION: Our findings provide insights into the effectiveness of IVIg in treating autoimmune or inflammatory pathologies associated with the loss of B-cell tolerance. Furthermore, these data provide a model to explore the complexity of positive versus negative selection in B cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:133 |
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| Enthalten in: |
The Journal of allergy and clinical immunology - 133(2014), 1 vom: 18. Jan., Seite 181-8.e1-9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Séïté, Jean-François [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 13.03.2014 Date Revised 27.12.2013 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jaci.2013.08.042 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Séïté, Jean-François |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Intravenous immunoglobulin induces a functional silencing program similar to anergy in human B cells |
| 264 | 1 | |c 2014 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 13.03.2014 | ||
| 500 | |a Date Revised 27.12.2013 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Chronic inflammatory and autoimmune diseases are largely due to inappropriate response of hyperactive or autoreactive B cells. These autoreactive B cells can evade central tolerance checkpoints and migrate to the periphery, where they would be silenced by anergy. Such anergic cells are characterized by B-cell receptor (BCR) desensitization and altered downstream signaling | ||
| 520 | |a OBJECTIVE: We sought to determine whether intravenous immunoglobulin (IVIg) induces a nonresponsive state of B cells and to address the similarities of this mechanism to those described in anergy | ||
| 520 | |a METHODS: Human B cells were stimulated with anti-IgM antibody, and effects of IVIg on several parameters, such as calcium release, tyrosine phosphorylation, BCR aggregation, BCR internalization, or transcriptional activity, were studied by using flow cytometry, confocal microscopy, Western blotting, and a quantitative PCR array | ||
| 520 | |a RESULTS: IVIg-treated B cells show defects in activating coreceptor expression, calcium signaling, and BCR aggregation on engagement by antigen. IVIg also induces suppression of phosphoinositide 3-kinase signaling, which plays a central role in determining B-cell fate. All these events ultimately lead to profound modifications in gene expression, resulting in long-term functional but reversible silencing of IVIg-treated B cells | ||
| 520 | |a CONCLUSION: Our findings provide insights into the effectiveness of IVIg in treating autoimmune or inflammatory pathologies associated with the loss of B-cell tolerance. Furthermore, these data provide a model to explore the complexity of positive versus negative selection in B cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a B cells | |
| 650 | 4 | |a B-cell receptor | |
| 650 | 4 | |a BCR | |
| 650 | 4 | |a CTB | |
| 650 | 4 | |a Cholera toxin B | |
| 650 | 4 | |a FACS | |
| 650 | 4 | |a FITC | |
| 650 | 4 | |a Fluorescein isothiocyanate | |
| 650 | 4 | |a Fluorescence-activated cell sorting | |
| 650 | 4 | |a IVIg | |
| 650 | 4 | |a Intravenous immunoglobulin | |
| 650 | 4 | |a NF-κB | |
| 650 | 4 | |a NFAT | |
| 650 | 4 | |a Nuclear factor of activated T cells | |
| 650 | 4 | |a Nuclear factor κB | |
| 650 | 4 | |a PE | |
| 650 | 4 | |a PI3K | |
| 650 | 4 | |a PIP3 | |
| 650 | 4 | |a PTEN | |
| 650 | 4 | |a Phosphatase and tensin homolog | |
| 650 | 4 | |a Phosphatidylinositol (3,4,5)-trisphosphate | |
| 650 | 4 | |a Phosphoinositide 3-kinase | |
| 650 | 4 | |a Phosphotyrosine | |
| 650 | 4 | |a Phycoerythrin | |
| 650 | 4 | |a SA-IVIg | |
| 650 | 4 | |a SHIP | |
| 650 | 4 | |a SHP | |
| 650 | 4 | |a Sialylated intravenous immunoglobulin | |
| 650 | 4 | |a Src homology domain 2-containing inositol phosphatase | |
| 650 | 4 | |a Src homology domain 2-containing protein tyrosine phosphatase | |
| 650 | 4 | |a TRITC | |
| 650 | 4 | |a Tetrarhodamine isothiocyanate | |
| 650 | 4 | |a anergy | |
| 650 | 4 | |a autoimmunity | |
| 650 | 4 | |a chronic inflammatory diseases | |
| 650 | 4 | |a immune tolerance | |
| 650 | 4 | |a p-Tyr | |
| 650 | 7 | |a Antibodies, Anti-Idiotypic |2 NLM | |
| 650 | 7 | |a Immunoglobulins, Intravenous |2 NLM | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a Receptors, Antigen, B-Cell |2 NLM | |
| 650 | 7 | |a anti-IgM |2 NLM | |
| 700 | 1 | |a Goutsmedt, Carole |e verfasserin |4 aut | |
| 700 | 1 | |a Youinou, Pierre |e verfasserin |4 aut | |
| 700 | 1 | |a Pers, Jacques-Olivier |e verfasserin |4 aut | |
| 700 | 1 | |a Hillion, Sophie |e verfasserin |4 aut | |
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