Ocular immune privilege promoted by the presentation of peptide on tolerogenic B cells in the spleen. II. Evidence for presentation by Qa-1

Ocular immune privilege is the result of several unique features of the eye , including the systemic down-regulation of Th1 immune responses to Ags enc ountered in the anterior chamber of the eye-a phenomenon termed anterior ch amber-associated immune deviation (ACAID), The induction of ACAID requires the participation of three cell populations: the ocular ACAID APC, the sple nic B cell, and the splenic T cell. Because B cells have been implicated in tolerogenic Ag presentation in other systems, we hypothesized that B cells were responsible for the induction of regulatory T cells in ACAID. The cen tral hypothesis for this study is that APC from the eye migrate to the sple en where they release antigenic peptides (OVA) that are captured and presen ted to T cells by splenic B cells. A combination of in vitro and in vivo st udies demonstrated that splenic B cells, incubated with ACAID APC in vitro, were capable of inducing ACAID when transferred to naive mice. The inducti on of ACAID required the normal expression of beta (2)-microglobulin on bot h the B cell and ACAID APC, but not on the T suppressor cells. Moreover, th e induction of ACAID regulatory cells required histocompatibility between t he B cells and regulatory T cells at the TL/Qa region. The results indicate that: 1) B cells are necessary for the induction of ACAID; 2) ACAID B cell s do not directly suppress the expression of delayed-type hypersensitivity; and 3) the induction of Ag-specific regulatory T cells by ACAID B cells re quires histocompatibility at the TL/Qa region.