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

초록

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(hight) 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. (C) 2017 Elsevier Inc. All rights reserved.

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