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Cited by 503T-cell and B-cell ImmunologyImmune Response and InflammationPsoriasis: Treatment and Pathogenesis

The Development and Function of Regulatory B Cells Expressing IL-10 (B10 Cells) Requires Antigen Receptor Diversity and TLR Signals

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Yanaba, Koichi, Bouaziz, Jean-David, Matsushita, Takashi, Tsubata, Takeshi, Tedder, Thomas F·2009·The Journal of Immunology
DOI 10.4049/jimmunol.0900270PMC PMC3733128
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Abstract

Autoimmunity and inflammation are controlled in part by regulatory B cells, including a recently identified IL-10-competent CD1dhighCD5+ B cell subset termed B10 cells that represents 1–3% of adult mouse spleen B cells. In this study, pathways that influence B10 cell generation and IL-10 production were identified and compared with previously described regulatory B cells. IL-10-competent B cells were predominantly CD1dhighCD5+ in adult spleen and were the prevalent source of IL-10, but not other cytokines. B10 cell development and/or maturation in vivo required Ag receptor diversity and intact signaling pathways, but not T cells, gut-associated flora, or environmental pathogens. Spleen B10 cell frequencies were significantly expanded in aged mice and mice predisposed to autoimmunity, but were significantly decreased in mouse strains that are susceptible to exogenous autoantigen-induced autoimmunity. LPS, PMA, plus ionomycin stimulation in vitro for 5 h induced B10 cells to express cytoplasmic IL-10. However, prolonged LPS or CD40 stimulation (48 h) induced additional adult spleen CD1dhighCD5+ B cells to express IL-10 following PMA plus ionomycin stimulation. Prolonged LPS or CD40 stimulation of newborn spleen and adult blood or lymph node CD1dlow and/or CD5− B cells also induced cytoplasmic IL-10 competence in rare B cells, with CD40 ligation uniformly inducing CD5 expression. IL-10 secretion was induced by LPS signaling through MyD88-dependent pathways, but not following CD40 ligation. LPS stimulation also induced rapid B10 cell clonal expansion when compared with other spleen B cells. Thereby, both adaptive and innate signals regulate B10 cell development, maturation, CD5 expression, and competence for IL-10 production.

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  • Breg differentiation is influenced by signals such as CD40 ligation, TLR stimulation, and cytokine exposure.

    “Their differentiation is influenced by signals such as CD40 ligation, TLR stimulation, and cytokine exposure [58,63,64].”

    From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [64]

    The Discussion (page not provided) says CD40 signals may facilitate B10-cell maturation and that TLR signaling is critical for B10-cell effector function. It does not establish cytokine exposure as an influence on differentiation; it also says CD40 is not required for normal B10-cell development in vivo. (LLM, conf=0.86)

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Authors
Yanaba, K., Bouaziz, J.-D., Matsushita, T., Tsubata, T., & Tedder, T. F.
Affiliations
  • Duke Medical Center (US)
  • Tokyo Medical and Dental University (JP)
Corresponding author
  • Yanaba, Koichi
  • Matsushita, Takashi
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2009-06
Volume
182
Issue
12
Pages
7459-7472
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.0900270
PMC
PMC3733128
OpenAlex
W1790240239
Cited by
503
References
59
Citations by year
2026: 11 · 2025: 12 · 2024: 16 · 2023: 13 · 2022: 18 · 2021: 30 · 2020: 24 · 2019: 33 · 2018: 33 · 2017: 34 · 2016: 31 · 2015: 58 · 2014: 49 · 2013: 35 · 2012: 39
FWCI
15.24
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Philippe Foundation
  • National Institutes of Health (CA105001, AI057157, AI 56363)
  • National Cancer Institute (CA105001, CA96547, R01CA105001, R01CA096547)
  • National Institute of Allergy and Infectious Diseases (AI 057157, U54AI057157, U19AI056363, AI-56363)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords
regulatory B cells, B10 cells, IL-10, antigen receptor diversity, Toll-like receptor signaling, LPS, CD40 ligation, MyD88, autoimmunity, clonal expansion, B cell development, CD5 expression, aging
MeSH terms
Animals, B-Lymphocytes, Cell Differentiation, Cells, Cultured, Cytoplasm, Humans, Lipopolysaccharides, Receptors, Antigen, B-Cell, T-Lymphocytes, Signal Transduction, Autoimmunity, Interleukin-10, Mice, Knockout, CD5 Antigens, CD40 Antigens, Toll-Like Receptors, Mice, Myeloid Differentiation Factor 88, Antigens, CD1d

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