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

作者：Inui Masanori; Sugahara Tobinai Akiko; Fujii Hiroshi; Itoh Nakadai Ari; Fukuyama Hidehiro; Kurosaki Tomohiro; Ishii Tomonori; Harigae Hideo; Takai Toshiyuki

来源：International Immunology, 2016, 28(12): 597-604.

DOI：10.1093/intimm/dxw044

• autoimmunity
• B-cell development
• plasma cell
• tolerance

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 V-H 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 popwulations upon activation of memory B cells in vitro. B4 expression was found to be induced efficiently by IL-2, while IFN-alpha 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.

• 出版日期2016-12