TY - JOUR
T1 - Tolerogenic immunoreceptor ILT3/LILRB4 paradoxically marks pathogenic auto-antibodyproducing plasmablasts and plasma cells in non-treated SLE
AU - Inui, Masanori
AU - Sugahara-Tobinai, Akiko
AU - Fujii, Hiroshi
AU - Itoh-Nakadai, Ari
AU - Fukuyama, Hidehiro
AU - Kurosaki, Tomohiro
AU - Ishii, Tomonori
AU - Harigae, Hideo
AU - Takai, Toshiyuki
N1 - Funding Information:
This work was supported by research grants from the CREST Program of the Japan Science and Technology Agency, Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (24249016, 24659215, 16H05201) and a grant from Astellas Pharma Inc. The authors thank Nicholas Halewood for editorial assistance.
Publisher Copyright:
© The Japanese Society for Immunology. 2016. All rights reserved.
PY - 2016/12
Y1 - 2016/12
N2 - 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.
AB - 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.
KW - Autoimmunity
KW - B-cell development
KW - Plasma cell
KW - Tolerance
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U2 - 10.1093/intimm/dxw044
DO - 10.1093/intimm/dxw044
M3 - Article
C2 - 27742834
AN - SCOPUS:85014482201
VL - 28
SP - 597
EP - 604
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 12
ER -