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Cited by 1,574T-cell and B-cell ImmunologySystemic Lupus Erythematosus ResearchRheumatoid Arthritis Research and Therapies

CD19+CD24hiCD38hi B Cells Exhibit Regulatory Capacity in Healthy Individuals but Are Functionally Impaired in Systemic Lupus Erythematosus Patients

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Blair, Paul A., Noreña, Lina Yassin, Flores-Borja, Fabian, Rawlings, David J., Isenberg, David A., Ehrenstein, Michael R., Mauri, Claudia·2010·Immunity
DOI 10.1016/j.immuni.2009.11.009
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Abstract

The immunosuppressive function of regulatory B cells has been shown in several murine models of chronic inflammation, including collagen-induced arthritis, inflammatory bowel disease, and experimental autoimmune encephalomyelitis. Despite interest in these cells, their relevance to the maintenance of peripheral tolerance in humans remains elusive. Here, we demonstrate that human CD19(+)CD24(hi)CD38(hi) B cells possessed regulatory capacity. After CD40 stimulation, CD19(+)CD24(hi)CD38(hi) B cells suppressed the differentiation of T helper 1 cells, partially via the provision of interleukin-10 (IL-10), but not transforming growth factor-beta (TGF-beta), and their suppressive capacity was reversed by the addition of CD80 and CD86 mAbs. In addition, CD19(+)CD24(hi)CD38(hi) SLE B cells isolated from the peripheral blood of systemic lupus erythematosus (SLE) patients were refractory to further CD40 stimulation, produced less IL-10, and lacked the suppressive capacity of their healthy counterparts. Altered cellular function within this compartment may impact effector immune responses in SLE and other autoimmune disorders.

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  • Bregs inhibit the expansion of pathogenic T cells and other pro-inflammatory immune cells, thereby preventing excessive immune activation.

    “Bregs inhibit the expansion of pathogenic T cells and other pro-inflammatory immune cells, thereby preventing excessive immune activation [55 -58].”

    From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [57]

    The Discussion reports that human CD19+CD24hiCD38hi B cells inhibit differentiation of proinflammatory cytokine–expressing CD4+ T cells, supporting the claim’s general regulatory point. It does not establish inhibition of T-cell expansion or of other pro-inflammatory immune cells, and the reported experiments concern cells from healthy individuals rather than Bregs generally. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The proportion of Bregs ranges from 1 to 3% of total B cells in the spleen and peritoneal cavity of healthy mice, whereas in humans Bregs typically constitute 1-4% of circulating B cells under homeostatic conditions.

    “The proportion of Bregs ranges from 1 to 3% of total B cells in the spleen and peritoneal cavity of healthy mice, whereas in humans, Bregs typically constitute 1 -4% of circulating B cells under homeostatic conditions [57,59,60].”

    From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [57]

    The Results identify regulatory CD19+CD24hiCD38hi B cells in the peripheral blood of healthy human donors. The passages do not give the claimed 1–4% frequency in humans or the 1–3% frequency in the spleen and peritoneal cavity of healthy mice; searches for those ranges and sites found no supporting passage. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Bregs are B cells with regulatory and immunosuppressive functions that maintain immunological homeostasis by producing IL-10, IL-35, and TGFβ, thereby suppressing immunopathology.

    “Bregs is a generic term used to define B cells endowed with regulatory and immunosuppressive functions. They play a crucial role in maintain­ ing immunological homeostasis by producing anti-inflammatory cyto­ kines such as interleukin-10 (IL-10), IL-35, and transforming growth factor-beta (TGFβ ), thereby suppressing immunopathology.”

    From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [57]

    The Results report that human regulatory B cells suppress CD4+ T-cell inflammatory responses partly through IL-10, supporting their regulatory function. But the same section finds suppression is not dependent on TGF-β, and the passages found do not identify IL-35 as a mediator. The paper therefore does not support the full three-cytokine account. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Blair, P. A., Noreña, L. Y., Flores-Borja, F., Rawlings, D. J., Isenberg, D. A., Ehrenstein, M. R., & Mauri, C.
Affiliations
  • University College London (GB)
  • University of Washington (US)
Corresponding author
Mauri, Claudia
ORCID
Venue
Immunity
Publisher
Elsevier BV
Published
2010-01
Volume
32
Issue
1
Pages
129-140
ISSN
1074-7613 (ISSN-L)
DOI
10.1016/j.immuni.2009.11.009
OpenAlex
W2088328410
Cited by
1,574
References
0
Citations by year
2026: 53 · 2025: 53 · 2024: 78 · 2023: 60 · 2022: 86 · 2021: 115 · 2020: 109 · 2019: 125 · 2018: 133 · 2017: 108 · 2016: 135 · 2015: 120 · 2014: 132 · 2013: 99 · 2012: 83
FWCI
36.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
Funders
Versus Arthritis (19314)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Keywords
regulatory B cells, systemic lupus erythematosus, CD40 stimulation, IL-10, CD80, CD86, peripheral tolerance, autoimmune disease
MeSH terms
Adult, Aged, B-Lymphocytes, Cell Differentiation, Cell Separation, Female, Flow Cytometry, Humans, Lupus Erythematosus, Systemic, Male, Middle Aged, Signal Transduction, B-Lymphocyte Subsets, Cytokines, Th1 Cells, Antigens, CD19, CD24 Antigen, ADP-ribosyl Cyclase 1, Young Adult

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