Human IL-10-producing B cells have diverse states that are induced from multiple B cell subsets

Marla C Glass; David R Glass; John-Paul Oliveria; Berenice Mbiribindi; Carlos O Esquivel; Sheri M Krams; Sean C Bendall; Olivia M Martinez

doi:10.1016/j.celrep.2022.110728

Human IL-10-producing B cells have diverse states that are induced from multiple B cell subsets

Cell Rep. 2022 Apr 19;39(3):110728. doi: 10.1016/j.celrep.2022.110728.

Authors

Marla C Glass¹, David R Glass², John-Paul Oliveria³, Berenice Mbiribindi¹, Carlos O Esquivel⁴, Sheri M Krams¹, Sean C Bendall⁵, Olivia M Martinez⁶

Affiliations

¹ Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA; Immunology, Stanford University School of Medicine, Stanford, CA, USA.
² Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Immunology Graduate Program, Stanford University, Stanford, CA, USA.
³ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Department of Medicine, Division of Respirology, McMaster University, Hamilton, ON, Canada.
⁴ Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA; Immunology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: omm@stanford.edu.

Abstract

Regulatory B cells (Bregs) suppress immune responses through the secretion of interleukin-10 (IL-10). This immunomodulatory capacity holds therapeutic potential, yet a definitional immunophenotype for enumeration and prospective isolation of B cells capable of IL-10 production remains elusive. Here, we simultaneously quantify cytokine production and immunophenotype in human peripheral B cells across a range of stimulatory conditions and time points using mass cytometry. Our analysis shows that multiple functional B cell subsets produce IL-10 and that no phenotype uniquely identifies IL-10⁺ B cells. Further, a significant portion of IL-10⁺ B cells co-express the pro-inflammatory cytokines IL-6 and tumor necrosis factor alpha (TNFα). Despite this heterogeneity, operationally tolerant liver transplant recipients have a unique enrichment of IL-10⁺, but not TNFα⁺ or IL-6⁺, B cells compared with transplant recipients receiving immunosuppression. Thus, human IL-10-producing B cells constitute an induced, transient state arising from a diversity of B cell subsets that may contribute to maintenance of immune homeostasis.

Keywords: B cells; Breg; CP: Immunology; IL-10; human; mass cytometry; single cell.

MeSH terms

B-Lymphocytes, Regulatory*
Cytokines
Humans
Immune Tolerance
Interleukin-10 / biosynthesis*
Interleukin-10 / genetics
Interleukin-6
Tumor Necrosis Factor-alpha

Substances

Cytokines
IL10 protein, human
Interleukin-6
Tumor Necrosis Factor-alpha
Interleukin-10

Abstract

MeSH terms

Substances

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