Spatiotemporal segregation of human marginal zone and memory B cell populations in lymphoid tissues. Homo sapiens

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 demonstrate phenotypic progression within lymphoid tissues as MZ B cells emerge from the mature naïve B cell pool via a precursor CD27-CD45RB[MEM55+] population distant from memory cells. By imaging mass cytometry, we show 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 they 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.