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

Jacqueline H Y Siu; Michael J Pitcher; Thomas J Tull; Rebekah L Velounias; William Guesdon; Lucia Montorsi; Krishnaa T Mahbubani; Richard Ellis; Pawan Dhami; Katrina Todd; Ulrich D Kadolsky; Michelle Kleeman; David P D'Cruz; Kourosh Saeb-Parsy; Mats Bemark; Gavin J Pettigrew; Jo Spencer

doi:10.1126/sciimmunol.abm9060

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

Jacqueline H Y Siu, Michael J Pitcher, Thomas J Tull, Rebekah L Velounias, William Guesdon, Lucia Montorsi, Krishnaa T Mahbubani, Richard Ellis, Pawan Dhami, Katrina Todd, Ulrich D Kadolsky, Michelle Kleeman, David P D'Cruz, Kourosh Saeb-Parsy, Mats Bemark, Gavin J Pettigrew, Jo Spencer

Research output: Contribution to journal › Article › peer-review

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 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 language	English
Pages (from-to)	eabm9060
Journal	Science Immunology
Volume	7
Issue number	69
DOIs	https://doi.org/10.1126/sciimmunol.abm9060
Publication status	Published - 18 Mar 2022

Keywords

B-Lymphocytes
Humans
Lymphocyte Activation
Lymphocyte Count
Lymphoid Tissue
Spleen

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1126/sciimmunol.abm9060

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Siu, J. H. Y., Pitcher, M. J., Tull, T. J., Velounias, R. L., Guesdon, W., Montorsi, L., Mahbubani, K. T., Ellis, R., Dhami, P., Todd, K., Kadolsky, U. D., Kleeman, M., D'Cruz, D. P., Saeb-Parsy, K., Bemark, M., Pettigrew, G. J., & Spencer, J. (2022). Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood. Science Immunology, 7(69), eabm9060. https://doi.org/10.1126/sciimmunol.abm9060

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

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 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.",

keywords = "B-Lymphocytes, Humans, Lymphocyte Activation, Lymphocyte Count, Lymphoid Tissue, Spleen",

author = "Siu, {Jacqueline H Y} and Pitcher, {Michael J} and Tull, {Thomas J} and Velounias, {Rebekah L} and William Guesdon and Lucia Montorsi and Mahbubani, {Krishnaa T} and Richard Ellis and Pawan Dhami and Katrina Todd and Kadolsky, {Ulrich D} and Michelle Kleeman and D'Cruz, {David P} and Kourosh Saeb-Parsy and Mats Bemark and Pettigrew, {Gavin J} and Jo Spencer",

year = "2022",

month = mar,

day = "18",

doi = "10.1126/sciimmunol.abm9060",

language = "English",

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pages = "eabm9060",

journal = "Science Immunology",

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Siu, JHY, Pitcher, MJ , Tull, TJ , Velounias, RL , Guesdon, W , Montorsi, L, Mahbubani, KT, Ellis, R, Dhami, P, Todd, K, Kadolsky, UD, Kleeman, M, D'Cruz, DP, Saeb-Parsy, K, Bemark, M, Pettigrew, GJ & Spencer, J 2022, 'Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood', Science Immunology, vol. 7, no. 69, pp. eabm9060. https://doi.org/10.1126/sciimmunol.abm9060

TY - JOUR

T1 - Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood

AU - Siu, Jacqueline H Y

AU - Pitcher, Michael J

AU - Tull, Thomas J

AU - Velounias, Rebekah L

AU - Guesdon, William

AU - Montorsi, Lucia

AU - Mahbubani, Krishnaa T

AU - Ellis, Richard

AU - Dhami, Pawan

AU - Todd, Katrina

AU - Kadolsky, Ulrich D

AU - Kleeman, Michelle

AU - D'Cruz, David P

AU - Saeb-Parsy, Kourosh

AU - Bemark, Mats

AU - Pettigrew, Gavin J

AU - Spencer, Jo

PY - 2022/3/18

Y1 - 2022/3/18

N2 - 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.

AB - 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.

KW - B-Lymphocytes

KW - Humans

KW - Lymphocyte Activation

KW - Lymphocyte Count

KW - Lymphoid Tissue

KW - Spleen

U2 - 10.1126/sciimmunol.abm9060

DO - 10.1126/sciimmunol.abm9060

M3 - Article

C2 - 35302862

SN - 2470-9468

VL - 7

SP - eabm9060

JO - Science Immunology

JF - Science Immunology

IS - 69

ER -

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

Abstract

Keywords

UN SDGs

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