Integration of T helper and BCR signals governs enhanced plasma cell differentiation of memory B cells by regulation of CD45 phosphatase activity.

Autor:	Szodoray P; Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway; K.G. Jebsen Center for B Cell Malignancies, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: peter.szodoray@medisin.uio.no., Andersen TK; Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway; K.G. Jebsen Center for Influenza Vaccine Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Heinzelbecker J; Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway; K.G. Jebsen Center for B Cell Malignancies, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Imbery JF; Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway; K.G. Jebsen Center for B Cell Malignancies, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Huszthy PC; Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway., Stanford SM; Division of Rheumatology, Allergy and Immunology, Department of Medicine, University of California, San Diego, 9500 Gilman Drive MC #0656, La Jolla, CA 92093, USA., Bogen B; Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway; K.G. Jebsen Center for Influenza Vaccine Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Landsverk OB; Department of Pathology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway., Bottini N; Division of Rheumatology, Allergy and Immunology, Department of Medicine, University of California, San Diego, 9500 Gilman Drive MC #0656, La Jolla, CA 92093, USA., Tveita A; Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway; K.G. Jebsen Center for B Cell Malignancies, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Munthe LA; Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway; K.G. Jebsen Center for B Cell Malignancies, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Nakken B; Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway; K.G. Jebsen Center for B Cell Malignancies, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Aug 10; Vol. 36 (6), pp. 109525.
DOI:	10.1016/j.celrep.2021.109525
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu