Positive selection of type II collagen-reactive CD80highmarginal zone B cells in DBA/1 mice.
To investigate whether dysregulated selection of autoreactive marginal zone (MZ) B cells is involved in autoimmune diseases, we examined MZ B cell profile in multiple strains of mice, and found that type II collagen (CII)-reactive autoreactive CD80highMZ B cells spontaneously developed in the DBA/1, but not in C57BL/6 mice. CD80highMZ B cells that were characteristically found in DBA/1 mice expressed higher levels of TACI, SLAM3, and SLAM6 than the usual CD80lowMZ B cells. Notably, the CD80highMZ B cells were more sensitive to ibrutinib, a Bruton's tyrosine kinase inhibitor, than CD80lowMZ or follicular B cells and their transient depletion via intravenous injection of ibrutinib significantly delayed the induction of collagen-induced arthritis (CIA). In summary, we suggest that the positive selection of CII-reactive CD80highMZ B cells is a critical homeostatic process predisposing the DBA/1 mice to the CIA induction.
Division of Immunobiology, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 16419, Republic of Korea.
Chanho
C
Park
Division of Immunobiology, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 16419, Republic of Korea.
In Seong
IS
Kho
Division of Immunobiology, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 16419, Republic of Korea.
Jeong
J
In Yang
Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Centre, Korea Institute of Radiological & Medical Sciences, Nowon-gu, Seoul 01812, Republic of Korea.
Min-Jung
MJ
Kim
Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Centre, Korea Institute of Radiological & Medical Sciences, Nowon-gu, Seoul 01812, Republic of Korea.
Sunhoo
S
Park
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
Hoon-Suk
HS
Cha
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea. Electronic address: jaejoonlee.lee@samsung.com.
Jaejoon
J
Lee
Division of Immunobiology, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 16419, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea. Electronic address: tjkim@skku.edu.
Tae Jin
TJ
Kim
D000225:Adenine / Q000031:analogs & derivatives; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D024043:Collagen Type II / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D000071176:Signaling Lymphocytic Activation Molecule Family / Q000378:metabolism; D053303:Transmembrane Activator and CAML Interactor Protein / Q000378:metabolism
D018122:B7-1 Antigen; D024043:Collagen Type II; C498972:Ly9 protein, mouse; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D000071176:Signaling Lymphocytic Activation Molecule Family; C000604063:Slamf6 protein, mouse; C486361:Tnfrsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein; C551803:ibrutinib; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse; D000225:Adenine
Autoimmunity; Autoreactive B cell; CD80; Collagen-induced arthritis; DBA/1 mouse; Marginal zone B cell