Splenic B cells are required for tolerogenic antigen presentation in the induction of anterior chamber‐associated immune deviation (ACAID)

Abstract

Ocular immune privilege is the result of a number of protective mechanisms, including a specialized immune response to antigen encountered in the anterior chamber of the eye. Anterior chamber-associated immune deviation, or ACAID, is characterized by the antigen-specific, selective down-regulation of systemic cell-mediated and humoral immune responses. One current hypothesis of the initiation of ACAID predicts that ocular APC process antigen and then migrate out of the eye and to the spleen where various regulatory T-cell populations are generated. A novel in vitro model of the ACAID spleen was developed to study the cells involved in the generation of suppressed T-cell immunity. ACAID APC co-cultured with whole splenocytes or splenic B and T cells induced efferent suppressors of delayed-type hypersensitivity (DTH). However, ACAID APC co-cultured with splenic T cells did not generate efferent suppressors of DTH. The requirement for B cells was confirmed with B-cell knockout mice. ACAID APC co-cultured with splenocytes from B-cell knockout mice did not induce efferent suppressors of DTH. Moreover, ACAID could not be induced in B-cell knockout mice in vivo. The reconstitution of B-cell knockout mice with wild-type B cells restored ACAID. In summary, these data confirm the role for B cells in the splenic phase of ACAID. A putative mechanism predicts that ACAID APC release antigenic peptides to B cells in the spleen. B cells then present antigen in a tolerogenic manner leading to the generation of regulatory T cells.

Ocular Immune Privilege Promoted by the Presentation of Peptide on Tolerogenic B Cells in the Spleen. II. Evidence for Presentation by Qa-1

“…Based on these findings, we hypothesized that B cells generate ACAID by presenting antigenic peptides to T cells in the context of Qa-1. Previous studies had shown that ACAID is abrogated in B cell knockout mice and that reconstitution with normal, syngeneic B cells restores ACAID (9). Our hy of the eye with 100 g OVA.…”

“…into B celldeficient mice. This procedure was shown to effectively reconstitute B cell knockout mice (9).…”

“…However, an additional experiment was performed to rule out the possibility that the adoptively transferred ACAID B cells were acting as direct suppressors of DTH. We tested this possibility using a previously described in vitro model of the ACAID spleen (9). In this model, Ag-pulsed ACAID APCs are incubated for 5-7 days with spleen cell cultures containing both T cells and B cells.…”

“…In this model, Ag-pulsed ACAID APCs are incubated for 5-7 days with spleen cell cultures containing both T cells and B cells. The ensuing nonadherent T cell population contains cells capable of suppressing the expression of DTH (9). For these experiments, ACAID APCs were generated and placed into culture with normal, unfractionated spleen cells.…”

“…Subsequent studies have shown that B cells are also necessary for the development of ACAID (8). Recently, it has been shown that the splenic B cell is necessary for the in vitro generation of at least one population of ACAID regulatory T cells (9). In other models of tolerance, B cells induce CD8 ϩ suppressor T cells when peptides are presented in the context of the nonclassical class I molecule Qa-1 (10).…”