Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-018-06089-1
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Funding
- Medical Research Council of Great Britain [MR/L009382/1, MR/P021964/1, MR/R000964/1]
- Gates Cambridge Trust
- St. Thomas' Lupus Trust
- National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust
- King's College London
- National Institutes of Health (NIH) [R01AI104739]
- MRC [MC_PC_16048, G0800746, MR/L009382/1, MR/P021964/1, MR/R000964/1, MC_PC_12011, MR/M007669/1, MR/M022927/1] Funding Source: UKRI
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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 naive B cell pool via a precursor CD27(-)CD45RB(MEM55+) population distant from memory cells. By imaging mass cytometry, we find that MZ B cells and memory B cells occupy different microanatomical niches in organised 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.
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