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

Publication date: Available online 2 February 2017
Source:Clinical Immunology
Author(s): Chanho Park, In Seong Kho, Jeong In Yang, Min-Jung Kim, Sunhoo Park, Hoon-Suk Cha, Jaejoon Lee, Tae Jin Kim
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.



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