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Nat Commun ; 13(1): 3121, 2022 06 03.
Article in English | MEDLINE | ID: mdl-35660734

ABSTRACT

Regulatory B cells (Breg) are a heterogenous population with immune-modulating functions. The rarity of human IL-10+ Breg makes translational studies difficult. Here we report ex vivo expansion of human B cells with in vivo regulatory function (expBreg). CD154-stimulation of human CD19+ B cells drives >900-fold expansion of IL-10+ B cells that is maintained in culture for 14 days. Whilst expBreg-mediated suppressive function is partially dependent on IL-10 expression, CRISPR-mediated gene deletions demonstrate predominant roles for TIM-1 and CD154. TIM-1 regulates STAT3 signalling and modulates downstream suppressive function. In a clinically relevant humanised mouse model of skin transplantation, expBreg prolongs human allograft survival. Meanwhile, CD19+CD73-CD25+CD71+TIM-1+CD154+ Breg cells are enriched in the peripheral blood of human donors with cutaneous squamous cell carcinoma (SCC). TIM-1+ and pSTAT3+ B cells are also identified in B cell clusters within histological sections of human cutaneous SCC tumours. Our findings thus provide insights on Breg homoeostasis and present possible targets for Breg-related therapies.


Subject(s)
B-Lymphocytes, Regulatory , Carcinoma, Squamous Cell , Skin Neoplasms , Animals , Antigens, CD19/metabolism , Carcinoma, Squamous Cell/metabolism , Humans , Interleukin-10/metabolism , Lymphocyte Activation , Mice , STAT3 Transcription Factor/metabolism , Skin Neoplasms/metabolism
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