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J.Y. Niederkorn, M.E. Skelsey, E. Mayhew; Role of B Cells in Anterior Chamber-Associated Immune Deviation . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1052.
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Purpose: B cells are required for the induction of several forms of immune tolerance, including anterior chamber-associated immune deviation (ACAID). This study examined the role of the B cell as an ancillary antigen-presenting cell (APC) in the induction of ACAID. Methods: A combination of in vivo and in vitro models of ACAID were employed. Ovalbumin (OVA) was either injected into the anterior chamber of BALB/c mice or added to BALB/c ocular APC cultures. In vitro spleen cultures were used to evaluate the role of splenic B cells in the generation of ACAID regulatory cells that suppress delayed-type hypersensitivity (DTH). Suppression of DTH was detected using a conventional local adoptive transfer (LAT) assay in the mouse ear pinna. Results were analyzed by Students t-test for statistical significance. Results: ACAID could not be induced in B cell-deficient mice or with spleen cell cultures depleted of B cells by panning on antibody-coated plates or spleen cell cultures from B cell-deficient mice. Cell cultures utilizing semi-permeable membranes (transwell cultures) demonstrated that direct contact between antigen-pulsed ocular APC and splenic B cells was not necessary for the generation of ACAID regulatory cells. Other transwell experiments demonstrated that cell contact between ACAID B cells and CD8+ T cells was absolutely required for the generation of regulatory T cells that directly suppressed DTH. Additional experiments revealed that: 1) B cell receptor for the relevant antigen is required for the induction of ACAID in vitro and in vivo; 2) antigen must be internalized in the B cell by a chloroquine-sensitive pathway; and 3) B cells from TAP knockout mice cannot induce ACAID.Conclusions:The results are consistent with the proposition that splenic B cells act as an ancillary APCs for the induction of ACAID. These findings strongly suggest that antigen released by ocular APC is captured and internalized by splenic B cells that present the antigen to CD8+ T cells, which in turn differentiate into regulatory cells that suppress DTH.
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