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

Cell Rep. 2023 May 30;42(5):112512. doi: 10.1016/j.celrep.2023.112512. Epub 2023 May 16.

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.

Keywords: B cell receptor; CP: Immunology; IL21; STAT3; affinity maturation; dark and light zones; germinal centers; memory B cells; plasma cells; somatic hypermutation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • B-Lymphocytes*
  • Germinal Center
  • Plasma Cells
  • STAT3 Transcription Factor*
  • Signal Transduction

Substances

  • STAT3 Transcription Factor