Type II Collagen-Specific B Cells Induce Immune Tolerance in Th1-Skewed, Th2-Skewed, and Arthritis-Prone Strains of Mice.

Abstract

Antigen-specific regulatory T cells play key immune suppressive roles in autoimmune disease models and regulate the peripheral tolerance achieved via anterior chamber-associated immune deviation (ACAID). Articular cartilage has type II collagen (CII), which is a potent autoantigen protein in arthritis. There has not been much research on the clinical importance of CII-associated diseases. Moreover, the capability of CII to induce immune tolerance has not been previously assessed. We reported that delivery of CII either directly into the eye or via intravenous injection of CII-specific ACAID antigen presenting cells (APCs) can induce ACAID. Here, we hypothesized that peripheral tolerance can be induced following adoptive transfer of in vitro generated CII-specific ACAID B cells to naive mice. Delayed hypersensitivity (DTH) assays were used to assess the suppressive ability of adoptively transferred B cells. Immune responses of ACAID B cell-injected mice were significantly suppressed following challenges with CII as compared to positive controls. This effect was replicated in three different strains of mice (C57BL/6, BALB/c, and DBA/1). Thus, CII-specific ACAID B cells were able to induce immune tolerance in Th1-skewed, Th2-skewed, and arthritis-prone mice. ACAID B cell-mediated tolerance induced by CII could have therapeutic implications for the treatment of CII-mediated autoimmune diseases.