STAT3 signaling in B cells controls germinal center zone organization and recycling.

Cell reports 2023 May 30

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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. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

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. STAT3 signaling in B cells controls germinal center zone organization and recycling. Cell reports. 2023 May 30;42(5):112512