STAT3 Signaling in B Cells Controls Germinal Center Zone Organization and Recycling

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2023 May 18

PMID 37200190

Authors

Adam J Fike

Sathi Babu Chodisetti

Nathaniel E Wright

Kristen N Bricker

Phillip P Domeier

Mark Maienschein-Cline

Aaron M Rosenfeld

Sara A Luckenbill

Julia L Weber

Nicholas M Choi

Eline T Luning Prak

Malay Mandal

Marcus R Clark

Ziaur S M Rahman

Affiliations

Soon will be listed here.

Abstract

Germinal centers (GCs), sites of antibody affinity maturation, are organized into dark (DZ) and light (LZ) zones. Here, we show a B cell-intrinsic role for signal transducer and activator of transcription 3 (STAT3) in GC DZ and LZ organization. Altered zonal organization of STAT3-deficient GCs dampens development of long-lived plasma cells (LL-PCs) but increases memory B cells (MBCs). In an abundant antigenic environment, achieved here by prime-boost immunization, STAT3 is not required for GC initiation, maintenance, or proliferation but is important for sustaining GC zonal organization by regulating GC B cell recycling. Th cell-derived signals drive STAT3 tyrosine 705 and serine 727 phosphorylation in LZ B cells, regulating their recycling into the DZ. RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analyses identified STAT3 regulated genes that are critical for LZ cell recycling and transiting through DZ proliferation and differentiation phases. Thus, STAT3 signaling in B cells controls GC zone organization and recycling, and GC egress of PCs, but negatively regulates MBC output.

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