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

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

doi:10.1016/j.celrep.2022.110728

Cited by 29 publications

(30 citation statements)

References 73 publications

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“…Based on their impact on immune responses, B cells can be broadly separated into two functional groups. However, it is important to highlight there is significant plasticity within these functional groups, with reports over the last 40 years demonstrating that human B cells can often co-express IL-10 with the pro-inflammatory cytokines TNF and IL-6 [ 22 , 62–64 ], and with type 2 cytokines such as IL-4 and IL-12 [ 27 ]. These data demonstrate that many cytokine-producing B cell subsets are polyfunctional.…”

Section: Introductionmentioning

confidence: 99%

Cytokine production by human B cells: role in health and autoimmune disease

Gruijter

Jebson

Rosser

2022

Clinical and Experimental Immunology

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B cells are classically considered solely as antibody-producing cells driving humoral immune responses to foreign antigens in infections and vaccinations as well as self-antigens in pathological settings such as autoimmunity. However, it has now become clear that B cells can also secrete a vast array of cytokines, which influence both pro- and anti-inflammatory immune responses. Indeed – similarly to T cells – there is significant heterogeneity in cytokine-driven responses by B cells, ranging from the production of pro-inflammatory effector cytokines such as IL-6, through to the release of immunosuppressive cytokines such as IL-10. In this review, focusing on human B cells, we summarise the key findings that have revealed that cytokine-producing B cell subsets have critical functions in healthy immune responses and contribute to the pathophysiology of autoimmune diseases.

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Section: Introductionmentioning

confidence: 99%

Cytokine production by human B cells: role in health and autoimmune disease

Gruijter

Jebson

Rosser

2022

Clinical and Experimental Immunology

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“…Because the regulatory properties of B cells are not limited exclusively to the CD19 + CD24 high CD38 high subpopulation ( 55 , 56 ), we analyzed the frequencies of the IL-10-positive cells among the total pool of B lymphocytes after a short CpG stimulation. Such rapid stimulation (less than 24 hours) allows estimating IL-10 production only in Bregs and not in the B cells predisposed for the IL-10 expression.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, it results in either a diverse or restricted clonal repertoire, the latter being ensured by the clonally related Bregs. Moreover, almost any B cell can become a regulatory B cell at a certain stage of its development upon exposure to permissive environmental stimuli ( 35 , 55 ). In the present study, we focus on the repertoire of tBregs with the CD19 + CD24 high CD38 high phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, increased tBreg counts along with the absence of increased IL-10 production can serve as indirect evidence in favor of their disrupted functioning and altered inflammatory profile during MS development. We suggest that, in future studies, tBregs should be analyzed for IL-10 production as well as co-expression of other cytokines as IL-10 + B cells are previously shown to co-express pro-inflammatory cytokines such as IL-6 and tumor necrosis factor alpha (TNFa) ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

“…These inconsistencies most likely arise from several Breg populations coexisting ( 55 , 56 ). Indeed, these regulatory subpopulations can comprise B cells at different stages of development; therefore, the level of certain BCR hypermutations can be lower at the earlier stages of maturation of these B cells.…”

Section: Introductionmentioning

confidence: 99%

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Deconvolution of B cell receptor repertoire in multiple sclerosis patients revealed a delay in tBreg maturation

et al. 2022

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BackgroundB lymphocytes play a pivotal regulatory role in the development of the immune response. It was previously shown that deficiency in B regulatory cells (Bregs) or a decrease in their anti-inflammatory activity can lead to immunological dysfunctions. However, the exact mechanisms of Bregs development and functioning are only partially resolved. For instance, only a little is known about the structure of their B cell receptor (BCR) repertoires in autoimmune disorders, including multiple sclerosis (MS), a severe neuroinflammatory disease with a yet unknown etiology. Here, we elucidate specific properties of B regulatory cells in MS.MethodsWe performed a prospective study of the transitional Breg (tBreg) subpopulations with the CD19+CD24highCD38high phenotype from MS patients and healthy donors by (i) measuring their content during two diverging courses of relapsing-remitting MS: benign multiple sclerosis (BMS) and highly active multiple sclerosis (HAMS); (ii) analyzing BCR repertoires of circulating B cells by high-throughput sequencing; and (iii) measuring the percentage of CD27+ cells in tBregs.ResultsThe tBregs from HAMS patients carry the heavy chain with a lower amount of hypermutations than tBregs from healthy donors. The percentage of transitional CD24highCD38high B cells is elevated, whereas the frequency of differentiated CD27+ cells in this transitional B cell subset was decreased in the MS patients as compared with healthy donors.ConclusionsImpaired maturation of regulatory B cells is associated with MS progression.

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IL-10-providing B cells govern pro-inflammatory activity of macrophages and microglia in CNS autoimmunity

Geladaris

Häusser‐Kinzel²,

Pretzsch³

et al. 2023

Acta Neuropathol

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B cells contribute to chronic inflammatory conditions as source of antibody-secreting plasma cells and as antigen-presenting cells activating T cells, making anti-CD20-mediated B cell depletion a widely used therapeutic option. B cells or B cell subsets may, however, exert regulatory effects, while to date, the immunological and/or clinical impact of these observations remained unclear. We found that in multiple sclerosis (MS) patients, B cells contain regulatory features and that their removal enhanced activity of monocytes. Using a co-culture system, we identified B cell-provided interleukin (IL)-10 as key factor in controlling pro-inflammatory activity of peripheral myeloid cells as well as microglia. Depleting B cells via anti-CD20 in a mouse model of MS unleashed the activity of myeloid cells and microglia and accelerated disease severity; in contrast, adoptive transfer of IL-10-providing B cells restored in vivo control of central nervous system (CNS) macrophages and microglia and reversed clinical exacerbation. These findings suggest that B cells exert meaningful regulatory properties, which should be considered when designing novel B cell-directed agents.

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

Cited by 29 publications

References 73 publications

Cytokine production by human B cells: role in health and autoimmune disease

Cytokine production by human B cells: role in health and autoimmune disease

Deconvolution of B cell receptor repertoire in multiple sclerosis patients revealed a delay in tBreg maturation

IL-10-providing B cells govern pro-inflammatory activity of macrophages and microglia in CNS autoimmunity

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