Details

Autor(en) / Beteiligte

• Szodoray, Peter
• Andersen, Tor Kristian
• Heinzelbecker, Julia
• Imbery, John F.
• Huszthy, Peter C.
• Stanford, Stephanie M.
• Bogen, Bjarne
• Landsverk, Ole B.
• Bottini, Nunzio
• Tveita, Anders
• Munthe, Ludvig A.
• Nakken, Britt

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2021-08, Vol.36 (6), p.109525-109525, Article 109525

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Memory B cells (MBCs) have high CD45 phosphatase activity•CD45 phosphatase activity defines high-affinity plasma cell precursors•Effective ASC differentiation of MBCs depends on high CD45 phosphatase activity•CD40L upregulates CD45 phosphatase activity through surface binding of Galectin-1 Szodoray et al. demonstrate that T helper signals upregulate CD45 phosphatase activity in B cells through increased binding of Galectin-1 to CD45. High CD45 phosphatase activity in memory B cells controls their effective differentiation toward antibody-secreting cells in response to T cell help.