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

Author:

Krause RobertORCID,Ogongo PaulORCID,Tezera Liku,Ahmed Mohammed,Mbano Ian,Chambers Mark,Ngoepe Abigail,Magnoumba Magalli,Muema Daniel,Karim Farina,Khan KhadijaORCID,Lumamba Kapongo,Nargan Kievershen,Madansein Rajhmun,Steyn AdrieORCID,Shalek Alex K.ORCID,Elkington Paul,Leslie AlORCID

Abstract

AbstractB 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 patients with TB 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. Flow cytometry and transcriptomics identify 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 contain high levels of Mtb-reactive antibodies, specifically IgM, which promotes Mtb phagocytosis. Overall, these data reveal the presence of functionally diverse B cell subsets in the lungs of patients with TB and suggest several potential localized roles that may represent a target for interventions to promote immunity or mitigate immunopathology.

Funder

Wellcome Trust

Bill and Melinda Gates Foundation

RCUK | MRC | Medical Research Foundation

RCUK | Medical Research Council

Publisher

Springer Science and Business Media LLC

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