Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Self-tolerance curtails the B cell repertoire to microbial epitopes
Akiko Watanabe, … , E. William St. Clair, Garnett Kelsoe
Akiko Watanabe, … , E. William St. Clair, Garnett Kelsoe
Published May 16, 2019
Citation Information: JCI Insight. 2019;4(10):e122551. https://doi.org/10.1172/jci.insight.122551.
View: Text | PDF
Research Article Immunology

Self-tolerance curtails the B cell repertoire to microbial epitopes

  • Text
  • PDF
Abstract

Immunological tolerance removes or inactivates self-reactive B cells, including those that also recognize cross-reactive foreign antigens. Whereas a few microbial pathogens exploit these “holes” in the B cell repertoire by mimicking host antigens to evade immune surveillance, the extent to which tolerance reduces the B cell repertoire to foreign antigens is unknown. Here, we use single-cell cultures to determine the repertoires of human B cell antigen receptors (BCRs) before (transitional B cells) and after (mature B cells) the second B cell tolerance checkpoint in both healthy donors and in patients with systemic lupus erythematosus (SLE) . In healthy donors, the majority (~70%) of transitional B cells that recognize foreign antigens also bind human self-antigens (foreign+self), and peripheral tolerance halves the frequency of foreign+self-reactive mature B cells. In contrast, in SLE patients who are defective in the second tolerance checkpoint, frequencies of foreign+self-reactive B cells remain unchanged during maturation of transitional to mature B cells. Patterns of foreign+self-reactivity among mature B cells from healthy donors differ from those of SLE patients. We propose that immune tolerance significantly reduces the scope of the BCR repertoire to microbial pathogens and that cross-reactivity between foreign and self epitopes may be more common than previously appreciated.

Authors

Akiko Watanabe, Kuei-Ying Su, Masayuki Kuraoka, Guang Yang, Alexander E. Reynolds, Aaron G. Schmidt, Stephen C. Harrison, Barton F. Haynes, E. William St. Clair, Garnett Kelsoe

×

Figure 7

Inhibition of F+S-reactive IgGs by free foreign antigens.

Options: View larger image (or click on image) Download as PowerPoint
Inhibition of F+S-reactive IgGs by free foreign antigens.
Selected F+S-r...
Selected F+S-reactive IgGs were incubated with various concentrations of free, either specific or irrelevant (BSA) foreign antigens, and then binding to foreign antigens (homologous inhibition) and self-antigens (heterologous inhibition) was assessed by Luminex multiplex assay. Fixed concentrations of F+S-reactive IgGs (100 μg/ml for Ab5 in A, 500 μg/ml for Ab6 in B) were first incubated with the indicated concentrations of free HA/Wis-h (A, black lines) or HA/Joburg-h (B, black lines) or BSA (A and B, gray lines), and then these mixtures were added to a panel of antigen-bead conjugates. MFI values for each antigen-bead conjugate were normalized with those without free antigens that were set as 100%. Ab5 bound HA/Wis and HA/Wis-h, and human self-antigens, including RNP, dsDNA, Jo-1, Sm, HEp-2 NA, histone, Scl-70, SSB, and centromere B (Supplemental Figure 4). Ab6 bound HA/Joburg-h and self-antigens, including RNP, HEp-2NA, Sm, centromere B, Scl-70, dsDNA, and histone (Supplemental Figure 5).

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts