Spatiotemporal segregation of human marginal zone and memory B cell populations in lymphoid tissue

Yuan Zhao, Mohamed Uduman, Jacqueline Siu, Thomas Justin Tull, Jeremy Sanderson, Yu-Chang Bryan Wu, Julian Q Zhou, Nedyalko Petrov, Richard Jonathan Ellis, Sarah Katrina Todd, Konstantia-Maria Chavele, William Wilfried Jonathan Guesdon, Anna Vossenkamper, Wayel Jassem, David D’Cruz, David Jonathan Fear, Susan John, dagmar Scheel-Toellner, claire hopkins, Estefania MorenoNatalie Woodman, Francesca Donatella Ciccarelli, Susanne Heck, Steven Kleinstein, Mats Bemark, Jo Michele Spencer

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Abstract

Human memory B cells and marginal zone (MZ) B cells share common features such as the expression of CD27 and somatic mutations in their IGHV and BCL6 genes, but the relationship between them is controversial. Here, we show phenotypic progression within lymphoid tissues as MZ B cells emerge from the mature naïve B cell pool via a precursor CD27-CD45RBMEM55+ population distant from memory cells. By imaging mass cytometry, we find that MZ B cells and memory B cells occupy different microanatomical niches in organized gut lymphoid tissues. Both populations disseminate widely between distant lymphoid tissues and blood, and both diversify their IGHV repertoire in gut germinal centres (GC), but nevertheless remain largely clonally separate. MZ B cells are therefore not developmentally contiguous with or analogous to classical memory B cells despite their shared ability to transit through GC where somatic mutations are acquired.
Original languageEnglish
Article number3857
Number of pages15
JournalNature Communications
Volume9
Issue number1
Early online date21 Sept 2018
DOIs
Publication statusPublished - 21 Sept 2018

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