Distinctive humoral immune responses following anterior chamber and intravenous administration of soluble antigen. Evidence for active suppression of IgG2-secreting B lymphocytes

Abstract

Inoculation of soluble antigen into the anterior chamber (AC) of the eyes of mice and rats induces a distinctive form of immune deviation known as anterior chamber-associated immune deviation (ACAID). Similarly, intravenous injections of soluble antigen induce immune deviation. In both instances, a selective impairment of delayed hypersensitivity (DH) is observed, whereas humoral immunity is said to be preserved. Recently, we noted that radiolabelled bovine serum albumin (BSA) was not eliminated in an immune fashion from the blood of animals pretreated with this antigen via AC and intravenous (i.v.) routes of inoculation. This was puzzling because the sera of these animals contained easily measurable anti-BSA antibodies. We have examined the characteristics of the anti-BSA humoral responses of mice following i.v. and AC inoculation of BSA in order to understand the reason for the lack of immune elimination. The results indicate that AC and i.v. recipients fail to eliminate antigen in an immune fashion because they produce insufficient amounts of complement-fixing (IgG2) antibodies, even though the other isotypes of immunoglobulins are well represented in the humoral anti-BSA response. The pattern of antibody isotype production, especially after boosting with BSA in complete Freund's adjuvant (CFA), implies that activation of IgG2-secreting, BSA-specific B cells is suppressed. Evidence is presented demonstrating this suppression to be antigen-specific and mediated by CD8+ T lymphocytes. These data are compatible with the hypothesis that interleukin-4 (IL-4)-secreting T helper (Th) cells are selectively activated in ACAID, whereas interferon-gamma (IFN-gamma)IL-2-secreting Th cells are actively suppressed.