Integration of T helper and BCR signals governs enhanced plasma cell differentiation of memory B cells by regulation of CD45 phosphatase activity
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved..
Humoral immunity relies on the efficient differentiation of memory B cells (MBCs) into antibody-secreting cells (ASCs). T helper (Th) signals upregulate B cell receptor (BCR) signaling by potentiating Src family kinases through increasing CD45 phosphatase activity (CD45 PA). In this study, we show that high CD45 PA in MBCs enhances BCR signaling and is essential for their effective ASC differentiation. Mechanistically, Th signals upregulate CD45 PA through intensifying the surface binding of a CD45 ligand, Galectin-1. CD45 PA works as a sensor of T cell help and defines high-affinity germinal center (GC) plasma cell (PC) precursors characterized by IRF4 expression in vivo. Increasing T cell help in vitro results in an incremental CD45 PA increase and enhances ASC differentiation by facilitating effective induction of the transcription factors IRF4 and BLIMP1. This study connects Th signals with BCR signaling through Galectin-1-dependent regulation of CD45 PA and provides a mechanism for efficient ASC differentiation of MBCs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
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| Enthalten in: |
Cell reports - 36(2021), 6 vom: 10. Aug., Seite 109525 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Szodoray, Peter [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.02.2022 Date Revised 26.02.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2021.109525 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM329239392 |
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| 100 | 1 | |a Szodoray, Peter |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Integration of T helper and BCR signals governs enhanced plasma cell differentiation of memory B cells by regulation of CD45 phosphatase activity |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Humoral immunity relies on the efficient differentiation of memory B cells (MBCs) into antibody-secreting cells (ASCs). T helper (Th) signals upregulate B cell receptor (BCR) signaling by potentiating Src family kinases through increasing CD45 phosphatase activity (CD45 PA). In this study, we show that high CD45 PA in MBCs enhances BCR signaling and is essential for their effective ASC differentiation. Mechanistically, Th signals upregulate CD45 PA through intensifying the surface binding of a CD45 ligand, Galectin-1. CD45 PA works as a sensor of T cell help and defines high-affinity germinal center (GC) plasma cell (PC) precursors characterized by IRF4 expression in vivo. Increasing T cell help in vitro results in an incremental CD45 PA increase and enhances ASC differentiation by facilitating effective induction of the transcription factors IRF4 and BLIMP1. This study connects Th signals with BCR signaling through Galectin-1-dependent regulation of CD45 PA and provides a mechanism for efficient ASC differentiation of MBCs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a B cell memory | |
| 650 | 4 | |a B cell receptor signaling | |
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| 650 | 4 | |a CD45 phosphatase activity | |
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| 700 | 1 | |a Heinzelbecker, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Imbery, John F |e verfasserin |4 aut | |
| 700 | 1 | |a Huszthy, Peter C |e verfasserin |4 aut | |
| 700 | 1 | |a Stanford, Stephanie M |e verfasserin |4 aut | |
| 700 | 1 | |a Bogen, Bjarne |e verfasserin |4 aut | |
| 700 | 1 | |a Landsverk, Ole B |e verfasserin |4 aut | |
| 700 | 1 | |a Bottini, Nunzio |e verfasserin |4 aut | |
| 700 | 1 | |a Tveita, Anders |e verfasserin |4 aut | |
| 700 | 1 | |a Munthe, Ludvig A |e verfasserin |4 aut | |
| 700 | 1 | |a Nakken, Britt |e verfasserin |4 aut | |
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