Accumulation of peripheral autoreactive B cells in the absence of functional human regulatory T cells

Tuure Kinnunen, Nicolas Chamberlain, Henner Morbach, Jinyoung Choi, Sangtaek Kim, Joseph Craft, Lloyd Mayer, Caterina Cancrini, Laura Passerini, Rosa Bacchetta, Hans D. Ochs, Troy R. Torgerson, Eric Meffre

Research output: Contribution to journalArticle

Abstract

Regulatory T cells (Tregs) play an essential role in preventing autoimmunity. Mutations in the forkhead box protein 3 (FOXP3) gene, which encodes a transcription factor critical for Treg function, result in a severe autoimmune disorder and the production of various autoantibodies in mice and in IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) patients. However, it is unknown whether Tregs normally suppress autoreactive B cells. To investigate a role for Tregs in maintaining human B-cell tolerance, we tested the reactivity of recombinant antibodies isolated from single B cells isolated from IPEX patients. Characteristics and reactivity of antibodies expressed by new emigrant/transitional B cells from IPEX patients were similar to those from healthy donors, demonstrating that defective Treg function does not impact central B-cell tolerance. In contrast, mature naive B cells from IPEX patients often expressed autoreactive antibodies, suggesting an important role for Tregs in maintaining peripheral B-cell tolerance. T cells displayed an activated phenotype in IPEX patients, including their Treg-like cells, and showed up-regulation of CD40L, PD-1, and inducibl T-cell costimulator (ICOS), which may favor the accumulation of autoreactive mature naive B cells in these patients. Hence, our data demonstrate an essential role for Tregs in the establishment and the maintenance of peripheral B-cell tolerance in humans.

Original languageEnglish
Pages (from-to)1595-1603
Number of pages9
JournalBlood
Volume121
Issue number9
DOIs
Publication statusPublished - Feb 28 2013

Fingerprint

T-cells
Regulatory T-Lymphocytes
B-Lymphocytes
Cells
Antibodies
Forkhead Transcription Factors
T-Lymphocytes
CD40 Ligand
B-Lymphoid Precursor Cells
Autoimmunity
Autoantibodies
Transcription Factors
Up-Regulation
Maintenance
Tissue Donors
Genes
Phenotype
Mutation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Kinnunen, T., Chamberlain, N., Morbach, H., Choi, J., Kim, S., Craft, J., ... Meffre, E. (2013). Accumulation of peripheral autoreactive B cells in the absence of functional human regulatory T cells. Blood, 121(9), 1595-1603. https://doi.org/10.1182/blood-2012-09-457465

Accumulation of peripheral autoreactive B cells in the absence of functional human regulatory T cells. / Kinnunen, Tuure; Chamberlain, Nicolas; Morbach, Henner; Choi, Jinyoung; Kim, Sangtaek; Craft, Joseph; Mayer, Lloyd; Cancrini, Caterina; Passerini, Laura; Bacchetta, Rosa; Ochs, Hans D.; Torgerson, Troy R.; Meffre, Eric.

In: Blood, Vol. 121, No. 9, 28.02.2013, p. 1595-1603.

Research output: Contribution to journalArticle

Kinnunen, T, Chamberlain, N, Morbach, H, Choi, J, Kim, S, Craft, J, Mayer, L, Cancrini, C, Passerini, L, Bacchetta, R, Ochs, HD, Torgerson, TR & Meffre, E 2013, 'Accumulation of peripheral autoreactive B cells in the absence of functional human regulatory T cells', Blood, vol. 121, no. 9, pp. 1595-1603. https://doi.org/10.1182/blood-2012-09-457465
Kinnunen T, Chamberlain N, Morbach H, Choi J, Kim S, Craft J et al. Accumulation of peripheral autoreactive B cells in the absence of functional human regulatory T cells. Blood. 2013 Feb 28;121(9):1595-1603. https://doi.org/10.1182/blood-2012-09-457465
Kinnunen, Tuure ; Chamberlain, Nicolas ; Morbach, Henner ; Choi, Jinyoung ; Kim, Sangtaek ; Craft, Joseph ; Mayer, Lloyd ; Cancrini, Caterina ; Passerini, Laura ; Bacchetta, Rosa ; Ochs, Hans D. ; Torgerson, Troy R. ; Meffre, Eric. / Accumulation of peripheral autoreactive B cells in the absence of functional human regulatory T cells. In: Blood. 2013 ; Vol. 121, No. 9. pp. 1595-1603.
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