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

Siu, Jacqueline H Y ; Pitcher, Michael J ; Tull, Thomas J ; Velounias, Rebekah L ; Guesdon, William ; Montorsi, Lucia ; Mahbubani, Krishnaa T ; Ellis, Richard ; Dhami, Pawan and Todd, Katrina , et al. (2022) In Science Immunology 7(69). p.1-16
Abstract

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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
keywords
B-Lymphocytes, Humans, Lymphocyte Activation, Lymphocyte Count, Lymphoid Tissue, Spleen
in
Science Immunology
volume
7
issue
69
article number
eabm9060
pages
1 - 16
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85126695458
  • pmid:35302862
ISSN
2470-9468
DOI
10.1126/sciimmunol.abm9060
language
English
LU publication?
no
id
311e3315-5a6f-473a-9a0d-5f28455f8e73
date added to LUP
2023-11-16 12:35:55
date last changed
2024-04-14 16:58:38
@article{311e3315-5a6f-473a-9a0d-5f28455f8e73,
  abstract     = {{<p>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.</p>}},
  author       = {{Siu, Jacqueline H Y and Pitcher, Michael J and Tull, Thomas J and Velounias, Rebekah L and Guesdon, William and Montorsi, Lucia and Mahbubani, Krishnaa T and Ellis, Richard and Dhami, Pawan and Todd, Katrina and Kadolsky, Ulrich D and Kleeman, Michelle and D'Cruz, David P and Saeb-Parsy, Kourosh and Bemark, Mats and Pettigrew, Gavin J and Spencer, Jo}},
  issn         = {{2470-9468}},
  keywords     = {{B-Lymphocytes; Humans; Lymphocyte Activation; Lymphocyte Count; Lymphoid Tissue; Spleen}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{69}},
  pages        = {{1--16}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Immunology}},
  title        = {{Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood}},
  url          = {{http://dx.doi.org/10.1126/sciimmunol.abm9060}},
  doi          = {{10.1126/sciimmunol.abm9060}},
  volume       = {{7}},
  year         = {{2022}},
}