Positive selection of type II collagen-reactive CD80high marginal zone B cells in DBA/1 mice

Chanho Park; In Seong Kho; Jeong In Yang; Min-Jung Kim; Sunhoo Park; Hoon-Suk Cha; Jaejoon Lee; Tae Jin Kim

doi:10.1016/j.clim.2017.01.015

Positive selection of type II collagen-reactive CD80^high marginal zone B cells in DBA/1 mice

Clin Immunol. 2017 May:178:64-73. doi: 10.1016/j.clim.2017.01.015. Epub 2017 Feb 2.

Authors

Chanho Park¹, In Seong Kho¹, Jeong In Yang¹, Min-Jung Kim², Sunhoo Park², Hoon-Suk Cha³, Jaejoon Lee⁴, Tae Jin Kim⁵

Affiliations

¹ Division of Immunobiology, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 16419, Republic of Korea.
² Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Centre, Korea Institute of Radiological & Medical Sciences, Nowon-gu, Seoul 01812, Republic of Korea.
³ Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
⁴ Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea. Electronic address: [email protected].
⁵ 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: [email protected].

PMID: 28163195
DOI: 10.1016/j.clim.2017.01.015

Abstract

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 CD80^high MZ B cells spontaneously developed in the DBA/1, but not in C57BL/6 mice. CD80^high MZ B cells that were characteristically found in DBA/1 mice expressed higher levels of TACI, SLAM3, and SLAM6 than the usual CD80^low MZ B cells. Notably, the CD80^high MZ B cells were more sensitive to ibrutinib, a Bruton's tyrosine kinase inhibitor, than CD80^low MZ 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 CD80^high MZ B cells is a critical homeostatic process predisposing the DBA/1 mice to the CIA induction.

Keywords: Autoimmunity; Autoreactive B cell; CD80; Collagen-induced arthritis; DBA/1 mouse; Marginal zone B cell.

MeSH terms

Adenine / analogs & derivatives
Agammaglobulinaemia Tyrosine Kinase
Animals
Arthritis, Experimental / immunology*
Autoimmunity / immunology
B-Lymphocytes / drug effects
B-Lymphocytes / immunology*
B-Lymphocytes / metabolism
B7-1 Antigen / metabolism
Cell Survival / immunology
Collagen Type II / immunology*
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Enzyme-Linked Immunospot Assay
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Piperidines
Protein Kinase Inhibitors / pharmacology
Protein-Tyrosine Kinases / antagonists & inhibitors
Pyrazoles / pharmacology
Pyrimidines / pharmacology
Signaling Lymphocytic Activation Molecule Family / metabolism
Transmembrane Activator and CAML Interactor Protein / metabolism

Substances

B7-1 Antigen
Collagen Type II
Ly9 protein, mouse
Piperidines
Protein Kinase Inhibitors
Pyrazoles
Pyrimidines
Signaling Lymphocytic Activation Molecule Family
Slamf6 protein, mouse
Tnfrsf13b protein, mouse
Transmembrane Activator and CAML Interactor Protein
ibrutinib
Protein-Tyrosine Kinases
Agammaglobulinaemia Tyrosine Kinase
Btk protein, mouse
Adenine