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

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 dif-ferentiation phases. Thus, STAT3 signaling in B cells controls GC zone organization and recycling, and GC egress of PCs, but negatively regulates MBC output.

Automated summary

This study reveals the important role of signal transducer and activator of transcription 3 (STAT3) in germinal centers (GCs). STAT3 deficiency alters GC structure, reducing the development of long-lived plasma cells (LL-PCs) but increasing the number of memory B cells (MBCs). STAT3 regulates GC B cell recycling, maintaining GC zone organization and controlling GC egress of plasma cells while negatively regulating MBC output.