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

Autor: Peter Szodoray, Tor Kristian Andersen, Julia Heinzelbecker, John F. Imbery, Peter C. Huszthy, Stephanie M. Stanford, Bjarne Bogen, Ole B. Landsverk, Nunzio Bottini, Anders Tveita, Ludvig A. Munthe, Britt Nakken
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cell Reports, Vol 36, Iss 6, Pp 109525- (2021)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2021.109525
Popis: Summary: 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.
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