Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood

Jo Spencer, Jacqueline Siu, Michael Pitcher, Thomas Tull, Rebekah Velounias, William Guesdon, Lucia Montorsi, Krishnaa Mahbubani, Richard Ellis, ulrich kadolsky, Michelle Kleeman, David D'Cruz, Kuorosh Saeb-Parsy, Mats Bemark, Gavin Pettigrew

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20 Citations (Scopus)
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B cells generate antibodies that are essential for immune protection, but their subgroups are poorly defined. Here, we perform undirected deep profiling of B cells in matched human lymphoid tissues from deceased transplant organ donors and blood. In addition to identifying unanticipated features of tissue-based B cell differentiation, we resolve two subsets of marginal zone B (MZB) cells differing in cell surface and transcriptomic profiles, clonal relationships to other subsets, enrichment of genes in the NOTCH pathway, distribution bias within splenic marginal zone microenvironment, and immunoglobulin repertoire diversity and hypermutation frequency. Each subset is present in spleen, gut-associated lymphoid tissue, mesenteric lymph nodes, and blood. MZB cells and the lineage from which they are derived are depleted in lupus nephritis. Here, we show that this depletion is of only one MZB subset. The other remains unchanged as a proportion of total B cells compared with health. Thus, it is important to factor MZB cell heterogeneity into studies of human B cell responses and pathology.

Original languageEnglish
Pages (from-to)eabm9060
JournalScience Immunology
Issue number69
Early online date18 Mar 2022
Publication statusPublished - 18 Mar 2022


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