期刊
SCIENCE IMMUNOLOGY
卷 7, 期 69, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.abm9060
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资金
- Wellcome Trust [220872/Z/20/Z]
- Medical Research Council of Great Britain [MR/R000964/1, MR/P021964/1]
- Lupus Trust
- Gates Cambridge Trust
- Canadian Centennial Scholarship Fund
- Swedish Research Council
- County Council of Vastra Gotaland
- CancerResearch UK KHP Cancer Centre
- Chan Zuckerberg Initiative
- Wellcome Trust [220872/Z/20/Z] Funding Source: Wellcome Trust
- MRC [MR/P021964/1, MR/R000964/1] Funding Source: UKRI
This study provides a deep analysis of B cells in lymphoid tissues and blood of deceased organ donors, leading to the identification of two subsets of marginal zone B (MZB) cells with distinct features and roles in immune response and pathology, emphasizing the importance of considering MZB cell heterogeneity in studying human B cell responses.
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 trans-plant organ donors and blood. In addition to identifying unanticipated features of tissue-based B cell differentia-tion, 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.
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