The IgE response of New Zealand Black mice to ovalbumin: An age-acquired increase in suppressor activity

Abstract

New Zealand Black (NZB) mice, from 6 weeks to 10 months of age, were immunized with ovalbumin (OA) in alum and the subsequent IgG and IgE anti-OA response was quantitated by radioimmunoassay and passive cutaneous anaphylaxis. The generation of IgG anti-OA was similar in both young and old NZB mice. In contrast, there was a marked age-dependent decline in the production of IgE anti-OA. Indeed, the percentage of NZB mice producing IgE anti-OA was reduced from 100% at 6 weeks to 55% at 6 months. 10% at 8 months, and 0% at 9 months. Moreover the IgE anti-OA response of 6-week NZB mice was suppressed by transfer of 9-month, but not 1-, 3-, or 6-month-old NZB spleen cells. The suppression of IgE production in young mice was mediated by macrophages; transfer of either splenic T or B cells or injection of freeze-thawed spleen cells from donor 9-month NZB mice to young recipients did not alter the production of IgE anti-OA. Parallel studies in BALB/c mice did not reveal an age-dependent change in the anti-OA response. The absence of an IgE response in 9-month-old NZB mice could not be restored by radiation, with or without reconstitution with populations of young thymocytes, spleen cells, and/or bone marrow cells. However, the IgE anti-OA response of old NZB mice could be significantly restored by splenectomy followed by intravenous reconstitution with young spleen cells. These observations suggest that NZB mice develop an age-dependent increase in suppressor macrophage activity. This heightened macrophage suppressor activity does not appear to be critical in the primary development of autoimmunity but is important for understanding acquired regulatory defects in New Zealand mice.