Tolerogenic immunoreceptor ILT3/LILRB4 paradoxically marks pathogenic auto-antibodyproducing plasmablasts and plasma cells in non-treated SLE

Masanori Inui, Akiko Sugahara, Hiroshi Fujii, Ari Ito, Hidehiro Fukuyama, Tomohiro Kurosaki, Tomonori Ishii, Hideo Harigae, Toshiyuki Takai

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Plasmablasts and plasma cells (PBs and PCs) producing pathogenic auto-antibodies in patients with systemic autoimmune diseases could be a better target for specific therapies for the disease than general immunosuppression or pan- or activated B-cell targeting. Our previous study indicated that leukocyte immunoglobulin-like receptor (LILR) B4 (B4, also known as ILT3/LIR-5/CD85k), a tolerogenic receptor in antigen-presenting cells, is ectopically expressed on the PB/PC surface in healthy individuals. Here, we show that the enlarged population size of PBs/PCs with augmented B4 expression is characteristic in non-treated systemic lupus erythematosus (SLE). Paradoxically, the transcription frequency of the anti-double-strand DNA immunoglobulin-coding VH sequence in the B4+ population of non-treated SLE was significantly higher than that in B4- cells. B4+ and B4- PBs/PCs were suggested to be developmentally equivalent based on the simultaneous generation of these populations upon activation of memory B cells in vitro. B4 expression was found to be induced efficiently by IL-2, while IFN-α effectively induced B4+ PBs/PCs in vitro. Utilizing the elevated B4 will support opening a new avenue for identifying the mechanism for generation of, and additional molecular markers for, pathogenic cells.

Original languageEnglish
Pages (from-to)597-604
Number of pages8
JournalInternational immunology
Volume28
Issue number12
DOIs
Publication statusPublished - 2016 Dec

Keywords

  • Autoimmunity
  • B-cell development
  • Plasma cell
  • Tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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