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S.-M. Hsu, R. Mathew, C. G. Kan, J. Stein-Streilein; Requirement of Marginal Zone B Cells for Induction of Eye Induced Tolerance in Sensitized Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):832.
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© ARVO (1962-2015); The Authors (2016-present)
The cellular interactions involved in ACAID (anterior chamber associated immune deviation) are well studied by several groups. ACAID can be induced in both naïve and antigen primed mice. While it is known that ACAID induction of antigen specific T regulatory cells require marginal zone (MZ) B cells in unsensitized mice it is not known if the generation of ACAID in sensitized mice also requires MZ B cells. The purpose of this study was to determine if splenic B cells are required, and then to define the B cell population that is important in ACAID induction in sensitized mice.
Mice lacking B cells (µKO) and wt B6 mice were inoculated (a.c.) with OVA seven days after they were immunized with OVA in CFA (s.c.). A week later the mice were tested for their ability to develop DTH (delayed type hypersensitivity) in response to an ear challenge with the immunizing antigen. To determine the subset of B cells involved importance of splenic B cells required for ACAID, the µKO mice were reconstituted with either CD23+ or CD43+ follicular (FO) B cells or CD23-CD43-MZ B cells.
Sensitized µKO mice showed an increase in ear swelling compared to sensitized B6 wt mice, demonstrating loss of immune privilege. When the µKO mice were reconstituted with whole B cells or MZ B cells, but not FO B cells, from the spleen, ACAID was restored. This suggests that splenic MZ B cells of the spleen play a vital role in the generation of ACAID.
Our results show that splenic MZ B cells are required for the induction of tolerance in previously sensitized mice. Since CD1d reactive iNKT are required for ACAID induction in presensitized mice, the possibility arises that CD1d+ MZ B cells are required to interact with CD1d-reactive NKT cells in a fashion similar to what is reported for ACAID generation in naïve mice. Since individuals with immune inflammatory diseases are presensitized, further understanding of the mechanisms that regulate immune effector mechanisms in sensitized individuals may lead to novel approaches for treatment of autoimmune diseases.
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