Cells involved in the immune response. XXXIII. Antibody-forming cells in the popliteal lymph nodes in the immunized splenectomized rabbit following intravenous immunization and their subsequent dissemination to the thymus.
Rabbits were splenectomized (splx) and immunized intravenously (iv) with sheep erythrocytes (SRBC) 14 days later. At the height of the primary immune response on Day 8 postimmunization, significant numbers of plaque-forming cells (PFC), that is, antibody-forming cells (AFC) synthesizing and secreting antibodies, were detected in the popliteal lymph nodes (PLN) and lesser numbers were detected in the bone marrow and the circulation. No PFC were detected in any of the other lymphoid organs. Rabbits were sacrificed at 1, 2, 6, or 9 months post-primary iv immunization and cell cultures of the lymphoid organs were set up with the antigen, SRBC, to induce secondary immune responses in vitro. Only the PLN cells challenged with SRBC in vitro 1 month post-primary immunization generated PFC and only PLN and thymus cells generated PFC in vitro at the three other challenge periods, thus demonstrating the existence of memory cells in only these two lymphoid organs in the splx rabbits. Following in vivo secondary immunization iv with SRBC 2, 6, or 9 months post-primary iv immunization. PFC were consistently detected only in the PLN and the bone marrow and inconsistently in the circulation. No PFC were detected in the thymus or in any of the other lymphoid organs. Paradoxically, neither the bone marrow nor the circulating mononuclear cells of these rabbits generated PFC during in vitro culture with SRBC, whereas the thymus cells and the PLN cells generated many PFC in culture with SRBC. These results demonstrate that the thymus contains memory cells following primary immunization of the splx rabbit which are not accessible to particulate antigens injected intravenously, possibly due to a blood-thymus barrier to particulate antigen, and therefore cannot be activated in vivo into secondary antibody formation. The results also indicate that the AFC detected in the circulation and in the bone marrow following primary iv immunization, which do not generate PFC in antigen-stimulated cultures in vitro, are degenerating cells whereas the AFC in the PLN and thymus, which generate many PFC in antigen-stimulated cultures in vitro, constitute the noncirculating precursors of the long-lived memory cells in the splx rabbit. This role of the thymus and PLN as reservoirs for memory cells in the immunized splx rabbit is not influenced by nor is it a result of splx since the thymus and PLN have both been shown to be the major sources of memory cells, along with the spleen, in the immunized nonsplx rabbit.
D000818:Animals; D000921:Antibody-Producing Cells; D007114:Immunization; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007717:Knee; D008198:Lymph Nodes / Q000166:cytology; D011817:Rabbits; D013156:Splenectomy; D013950:Thymus Gland / Q000276:immunology; D013997:Time Factors