Splenic macrophages: antigen presenting cells for T1–2 antigens

Abstract

Thymus-independent antigens type 2 (T1–2) such as DNP-Ficoll or DNP-hydroxyethyl starch are selectively retained in mice and rats by a distinct population of macrophages in the marginal zone of the white pulp of the spleen and in the marginal sinus and septa and medulla of lymph nodes. There is suggestive evidence that the antibody response to the haptenic determinants, which is rapid in onset and persists for many weeks, is largely made by a sessile subpopulation of B cells in the spleen marginal zone characterized by the presence of surface IgM but lacking IgD. Splenectomy in adult mice, rats and humans greatly diminishes and delays the antibody response to DNP-Ficoll, but has no such effect on the response to thymus-dependent, or (in mice) to T1-1 immunogens. In humans, if DNP-Ficoll had been administered prior to splenectomy, a normal antibody response was made when the antigen was readministered after splenectomy, indicating that once the responding B cells had been stimulated they were no longer confined to the spleen. Experiments in mice showed that after elimination of B cells by irradiation, responsiveness to T1–2 antigens could be restored by spleen cells isolated as single-cell suspensions provided that the architecture of the spleen remained, but could not be restored if the mice had been splenectomized. This implies that both the spleen B cells and the marginal zone macrophages are required. Since administration of cyclophosphamide, which selectively depletes the marginal zone B cell subpopulation, abolished the antibody response to T1–2 antigens in mice and rats until this subpopulation recovered, the B cells which initiate the antibody response are presumably contained therein. The capacity to initiate a thymus-independent rapid IgM antibody response to multi-epitope polymeric bacterial capsular polysaccharides depends largely upon the spleen. If splenectomy is contemplated, primary immunization with such antigens should be undertaken before rather than after the spleen is removed.