The Rheumatologist
COVID-19 News
  • Connect with us:
  • Facebook
  • Twitter
  • LinkedIn
  • YouTube
  • Feed
  • Home
  • Conditions
    • Rheumatoid Arthritis
    • SLE (Lupus)
    • Crystal Arthritis
      • Gout Resource Center
    • Spondyloarthritis
    • Osteoarthritis
    • Soft Tissue Pain
    • Scleroderma
    • Vasculitis
    • Systemic Inflammatory Syndromes
    • Guidelines
  • Resource Centers
    • Ankylosing Spondylitis Resource Center
    • Gout Resource Center
    • Rheumatoid Arthritis Resource Center
    • Systemic Lupus Erythematosus Resource Center
  • Drug Updates
    • Biologics & Biosimilars
    • DMARDs & Immunosuppressives
    • Topical Drugs
    • Analgesics
    • Safety
    • Pharma Co. News
  • Professional Topics
    • Ethics
    • Legal
    • Legislation & Advocacy
    • Career Development
      • Certification
      • Education & Training
    • Awards
    • Profiles
    • President’s Perspective
    • Rheuminations
  • Practice Management
    • Billing/Coding
    • Quality Assurance/Improvement
    • Workforce
    • Facility
    • Patient Perspective
    • Electronic Health Records
    • Apps
    • Information Technology
    • From the College
    • Multimedia
      • Audio
      • Video
  • Resources
    • Issue Archives
    • ACR Convergence
      • Systemic Lupus Erythematosus Resource Center
      • Rheumatoid Arthritis Resource Center
      • Gout Resource Center
      • Abstracts
      • Meeting Reports
      • ACR Convergence Home
    • American College of Rheumatology
    • ACR ExamRheum
    • Research Reviews
    • ACR Journals
      • Arthritis & Rheumatology
      • Arthritis Care & Research
      • ACR Open Rheumatology
    • Rheumatology Image Library
    • Treatment Guidelines
    • Rheumatology Research Foundation
    • Events
  • About Us
    • Mission/Vision
    • Meet the Authors
    • Meet the Editors
    • Contribute to The Rheumatologist
    • Subscription
    • Contact
  • Advertise
  • Search
You are here: Home / Articles / Patients with Lupus: Plasmacytoid Dendritic Cells Fail to Induce Regulatory B Cells

Patients with Lupus: Plasmacytoid Dendritic Cells Fail to Induce Regulatory B Cells

May 9, 2016 • By Lara C. Pullen, PhD

  • Tweet
  • Email
Print-Friendly Version / Save PDF
Graphical Abstract Highlights: "The signals required for Breg cell differentiation in humans are currently unknown. Mauri and colleagues show that plasmacytoid dendritic cells, via the provision of IFN-a, govern the differentiation of immature B cells into regulatory B cells that restrain inflammation."

Graphical Abstract: The signals required for Breg cell differentiation in humans are currently unknown.

Regulatory B (Breg) cells appear to play a critical role in managing the immune system and maintaining homeostasis. In healthy individuals, Breg cells are generated in response to pro-inflammatory cytokines secreted, at least in part, by plasmacytoid dentricitic cells (pDCs). Thus, pDCs appear able to both initiate a pro-inflammatory response and trigger the differentiation of regulatory cells. Given this important interaction, it is not surprising that researchers have examined the role of both Breg cells and pDCs in inflammatory diseases. Although researchers have been closing in on the relationship between pDCs and Breg cells, until now, the signals required for Breg cell differentiation in humans have remained unknown.

You Might Also Like
  • Neutrophils & B Cells Create Unique Antibodies in Lupus Patients
  • Naive B Cells Activate & Expand During Lupus Flares
  • Study Reveals Role of IL-17–Secreting CD4+ T Cells in Lupus
Also By This Author
  • Atherosclerosis, Cardiovascular Disease More Common in Patients with Primary Sjögren’s Syndrome

Madhvi Menon, a graduate student at the University College London, and colleagues published their analysis of pDCs in the March 15 issue of Immunity.1 The authors began by investigating whether pDCs could, indeed, generate Breg cells. They found that, when compared with B cells stimulated with the toll-like receptor 9 (TLR9) agonist CpGC alone, stimulation with pDCs induced a four-fold enrichment of IL-10-producing B cells. Moreover, when the B cells were cultured with either CpGC or with pDCs plus CpGC, they found that B cells cultured with pDCs were able to suppress the differentiation of IFNɣ+CD4+ T cells and TNFα+CD4+ T cells. Thus, the investigators established that pDCs control the differentiation of immature B cells into CD24+CD38hi Breg cells or plasmablasts via the secretion of IFNα. The differentiated Breg cells were then able to use IL-10 to limit pDC production of IFNα.

ad goes here:advert-1
ADVERTISEMENT
SCROLL TO CONTINUE

“Next, we investigated whether the pDC-expanded CD24+CD38hi Breg cells were derived directly from immature B cells or whether pDCs upregulated the expression of CD24 and CD38 on mature and memory B cells,” explained the authors. They purified B cell subsets from the pDC-immature B cell coculture and then co-cultured the cells with anti-CD3 CD4+CD25- T cells.

“We found that the concentration of IFNα determines whether an immature B cell develops into a CD24+CD38hi Breg cell or a plasmablast,” write the authors in their discussion. “At lower concentrations of IFNα, B cells differentiate into both plasmablasts and CD24+CD38hi Breg cells, whereas at higher concentrations, the B cell response is channeled toward plasma cell maturation.”

ad goes here:advert-2
ADVERTISEMENT
SCROLL TO CONTINUE

When the investigators turned their attention to the CD24+CD38hi B cells in patients with systemic lupus erythematosus (SLE), they found that these patients had defective pDC-mediated expansion of CD24+CD38hi Breg cells. Specifically, patients with SLE had hyperactivated pDCs that failed to induce Breg cells. However, the exceptions to this observation were patients with SLE who responded to rituximab. This subset of patients displayed a normalized pDC-Breg cell interaction.

“Our data suggest that the immune regulatory feedback between CD24+CD38hi Breg cells and pDCs that is in place in healthy individuals is dysfunctional in SLE patients, but that this feedback is normalized in patients who respond to rituximab. It is tempting to suggest that when sufficient CD24+CD38hi Breg cells have been generated at a site of inflammation by IFNα+ pDCs or after CD40–CD40L interactions with T cells, for instance, Breg cells can then prevent pDCs from producing excessive IFNα that would otherwise drive chronic inflammation,” explained the authors.


Lara C. Pullen, PhD, is a medical writer based in the Chicago area.

ad goes here:advert-3
ADVERTISEMENT
SCROLL TO CONTINUE

Reference

  1. Menon M, Blair PA, Isenberg DA, et al. A regulatory feedback between plasmacytoid dendritic cells and regulatory B cells is aberrant in systemic lupus erythematosus. Immunity. 2016 Mar 15;44(3):683–697. doi: 10.1016/j.immuni.2016.02.012. Epub 2016 Mar 8.

Pages: 1 2 | Multi-Page

Filed Under: Conditions, SLE (Lupus) Tagged With: B cells, Breg cells, Inflammatory Disease, Lupus, plasmacytoid dentricitic cells, systemic lupus erythematosus (SLE)

You Might Also Like:
  • Neutrophils & B Cells Create Unique Antibodies in Lupus Patients
  • Naive B Cells Activate & Expand During Lupus Flares
  • Study Reveals Role of IL-17–Secreting CD4+ T Cells in Lupus
  • TNF-α Impairs Regulatory T Cells in Patients with Rheumatoid Arthritis

Meeting Abstracts

Browse and search abstracts from the ACR Convergence and ACR/ARP Annual Meetings going back to 2012.

Visit the Abstracts site »

American College of Rheumatology

Visit the official website for the American College of Rheumatology.

Visit the ACR »

ACR Convergence

Don’t miss rheumatology’s premier scientific meeting for anyone involved in research or the delivery of rheumatologic care or services.

Visit the ACR Convergence site »

The Rheumatologist newsmagazine reports on issues and trends in the management and treatment of rheumatic diseases. The Rheumatologist reaches 11,500 rheumatologists, internists, orthopedic surgeons, nurse practitioners, physician assistants, nurses, and other healthcare professionals who practice, research, or teach in the field of rheumatology.

About Us / Contact Us / Advertise / Privacy Policy / Terms of Use

  • Connect with us:
  • Facebook
  • Twitter
  • LinkedIn
  • YouTube
  • Feed

Copyright © 2006–2021 American College of Rheumatology. All rights reserved.

ISSN 1931-3268 (print)
ISSN 1931-3209 (online)

loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.