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B cell heterogeneity in human tuberculosis highlights compartment-specific phenotype and functional roles

B cell heterogeneity in human tuberculosis highlights compartment-specific phenotype and functional roles
B cell heterogeneity in human tuberculosis highlights compartment-specific phenotype and functional roles
B cells are important in tuberculosis (TB) immunity, but their role in the human lung is understudied. Here, we characterize B cells from lung tissue and matched blood of TB patients and found they are decreased in the blood and increased in the lungs, consistent with recruitment to infected tissue, where they are located in granuloma associated lymphoid tissue (GrALT). Flow cytometry and transcriptomics identified multiple B cell populations in the lung, including those associated with tissue resident memory, germinal centers, antibody secretion, proinflammatory atypical B cells, and regulatory B cells, some of which are expanded in TB disease. Additionally, TB lungs contained high levels of Mtb-reactive antibodies, specifically IgM, which promoted Mtb phagocytosis. Overall, these data reveal the presence of functionally diverse B cell subsets in TB diseased lung and suggest several potential localized roles that may represent a target for interventions to promote immunity or mitigate immunopathology.
2399-3642
Krause, Robert
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Ogongo, Paul
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Tezera, Liku
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Ahmed, Mohammed
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Mbano, Ian
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Chambers, Mark
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Ngoepe, Abigail
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Magnoumba, Magalli
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Muema, Daniel
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Karim, Farina
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Khan, Khadija
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Lumamba, Kapongo
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Nargan, Kievershen
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Madansein, Rajhmun
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Steyn, Adrie
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Shalek, Alex K.
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Elkington, Paul
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Leslie, Al
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Krause, Robert
de546548-24b9-47c7-9177-d8e125272c64
Ogongo, Paul
695adbcd-0e29-48e0-b6a2-4a42fad39175
Tezera, Liku
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Ahmed, Mohammed
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Mbano, Ian
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Chambers, Mark
9cc40b9e-18a2-45a0-8d75-3b2bd5ebb71a
Ngoepe, Abigail
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Magnoumba, Magalli
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Muema, Daniel
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Karim, Farina
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Khan, Khadija
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Lumamba, Kapongo
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Nargan, Kievershen
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Madansein, Rajhmun
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Steyn, Adrie
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Shalek, Alex K.
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Elkington, Paul
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Leslie, Al
84d4f578-f3c0-46cc-9c83-a8d9bb40c38c

Krause, Robert, Ogongo, Paul, Tezera, Liku, Ahmed, Mohammed, Mbano, Ian, Chambers, Mark, Ngoepe, Abigail, Magnoumba, Magalli, Muema, Daniel, Karim, Farina, Khan, Khadija, Lumamba, Kapongo, Nargan, Kievershen, Madansein, Rajhmun, Steyn, Adrie, Shalek, Alex K., Elkington, Paul and Leslie, Al (2024) B cell heterogeneity in human tuberculosis highlights compartment-specific phenotype and functional roles. Communications Biology.

Record type: Article

Abstract

B cells are important in tuberculosis (TB) immunity, but their role in the human lung is understudied. Here, we characterize B cells from lung tissue and matched blood of TB patients and found they are decreased in the blood and increased in the lungs, consistent with recruitment to infected tissue, where they are located in granuloma associated lymphoid tissue (GrALT). Flow cytometry and transcriptomics identified multiple B cell populations in the lung, including those associated with tissue resident memory, germinal centers, antibody secretion, proinflammatory atypical B cells, and regulatory B cells, some of which are expanded in TB disease. Additionally, TB lungs contained high levels of Mtb-reactive antibodies, specifically IgM, which promoted Mtb phagocytosis. Overall, these data reveal the presence of functionally diverse B cell subsets in TB diseased lung and suggest several potential localized roles that may represent a target for interventions to promote immunity or mitigate immunopathology.

Text
Krause et al., B cell heterogeneity in human tuberculosis highlights compartment-specific phenotype and functional roles - Accepted Manuscript
Available under License Creative Commons Attribution.
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More information

Published date: 6 March 2024
Additional Information: AL was supported by the Wellcome Trust (210662/Z/18/Z) and the BMGF (OPP1137006). RK and PE were supported by a Dorothy Temple Cross grant from the UK Medical Research Foundation (MRF-131-0002-RG-ELKI-C0850). PE was supported by the UK Medical Research Council (MR/P023754/1 and MR/W025728/1).

Identifiers

Local EPrints ID: 487882
URI: http://eprints.soton.ac.uk/id/eprint/487882
ISSN: 2399-3642
PURE UUID: a64353fb-b78a-4a2c-ba39-81d57bd3b40c
ORCID for Liku Tezera: ORCID iD orcid.org/0000-0002-7898-6709
ORCID for Paul Elkington: ORCID iD orcid.org/0000-0003-0390-0613

Catalogue record

Date deposited: 08 Mar 2024 17:32
Last modified: 10 Apr 2024 04:02

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Contributors

Author: Robert Krause
Author: Paul Ogongo
Author: Liku Tezera ORCID iD
Author: Mohammed Ahmed
Author: Ian Mbano
Author: Mark Chambers
Author: Abigail Ngoepe
Author: Magalli Magnoumba
Author: Daniel Muema
Author: Farina Karim
Author: Khadija Khan
Author: Kapongo Lumamba
Author: Kievershen Nargan
Author: Rajhmun Madansein
Author: Adrie Steyn
Author: Alex K. Shalek
Author: Paul Elkington ORCID iD
Author: Al Leslie

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