T-bet-expressing B cells contribute to the autoreactive plasma cell pool in Lyn-/- mice
© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH..
Systemic Lupus Erythematosus (SLE) is characterized by pathogenic autoantibodies against nucleic acid-containing antigens. Understanding which B-cell subsets give rise to these autoantibodies may reveal therapeutic approaches for SLE that spare protective responses. Mice lacking the tyrosine kinase Lyn, which limits B and myeloid cell activation, develop lupus-like autoimmune diseases characterized by increased autoreactive plasma cells (PCs). We used a fate-mapping strategy to determine the contribution of T-bet+ B cells, a subset thought to be pathogenic in lupus, to the accumulation of PCs and autoantibodies in Lyn-/- mice. Approximately, 50% of splenic PCs in Lyn-/- mice originated from T-bet+ cells, a significant increase compared to WT mice. In vitro, splenic PCs derived from T-bet+ B cells secreted both IgM and IgG anti-dsDNA antibodies. To determine the role of these cells in autoantibody production in vivo, we prevented T-bet+ B cells from differentiating into PCs or class switching in Lyn-/- mice. This resulted in a partial reduction in splenic PCs and anti-dsDNA IgM and complete abrogation of anti-dsDNA IgG. Thus, T-bet+ B cells make an important contribution to the autoreactive PC pool in Lyn-/- mice.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
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| Enthalten in: |
European journal of immunology - 53(2023), 8 vom: 14. Aug., Seite e2250300 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ottens, Kristina [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.08.2023 Date Revised 25.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/eji.202250300 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356376184 |
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| 245 | 1 | 0 | |a T-bet-expressing B cells contribute to the autoreactive plasma cell pool in Lyn-/- mice |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. | ||
| 520 | |a Systemic Lupus Erythematosus (SLE) is characterized by pathogenic autoantibodies against nucleic acid-containing antigens. Understanding which B-cell subsets give rise to these autoantibodies may reveal therapeutic approaches for SLE that spare protective responses. Mice lacking the tyrosine kinase Lyn, which limits B and myeloid cell activation, develop lupus-like autoimmune diseases characterized by increased autoreactive plasma cells (PCs). We used a fate-mapping strategy to determine the contribution of T-bet+ B cells, a subset thought to be pathogenic in lupus, to the accumulation of PCs and autoantibodies in Lyn-/- mice. Approximately, 50% of splenic PCs in Lyn-/- mice originated from T-bet+ cells, a significant increase compared to WT mice. In vitro, splenic PCs derived from T-bet+ B cells secreted both IgM and IgG anti-dsDNA antibodies. To determine the role of these cells in autoantibody production in vivo, we prevented T-bet+ B cells from differentiating into PCs or class switching in Lyn-/- mice. This resulted in a partial reduction in splenic PCs and anti-dsDNA IgM and complete abrogation of anti-dsDNA IgG. Thus, T-bet+ B cells make an important contribution to the autoreactive PC pool in Lyn-/- mice | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Satterthwaite, Anne B |e verfasserin |4 aut | |
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