SPLENIC B-CELLS ARE REQUIRED FOR TOLEROGENIC ANTIGEN PRESENTATION IN THE INDUCTION OF ANTERIOR CHAMBER-ASSOCIATED IMMUNE DEVIATION (ACAID)

Ocular immune privilege is the result of a number of protective mechan isms, including a specialized immune response to antigen encountered i n the anterior chamber of the eye. Anterior chamber-associated immune deviation, or ACAID, is characterized by the antigen-specific, selecti ve downregulation of systemic cell-mediated and humoral immune respons es. One current hypothesis of the initiation of ACAID predicts that oc ular APC process antigen and then migrate out of the eye and to the sp leen where various regulatory T-cell populations are generated. A nove l 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 effe rent suppressors of delayed-type hypersensitivity (DTH). However, ACAI D APC co-cultured with splenic T cells did not generate efferent suppr essors of DTH. The requirement for B cells was confirmed with B-cell k nockout mice. ACAID APC co-cultured with splenocytes from B-cell knock out mice did not induce efferent suppressors of DTH. Moreover, ACAID c ould not be induced in B-cell knockout mice in vivo. The reconstitutio n of B-cell knockout mice with wild-type B cells restored ACAID. In su mmary, 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.