Differential requirements for an intact spleen in induction and expression of B-cell-dependent immunity to Plasmodium chabaudi AS.
The requirement for an architecturally intact spleen in the afferent and efferent arms of immunity to the murine malaria parasite Plasmodium chabaudi AS was analyzed. C57BL/6 mice with intact spleens develop a single, patent parasitemia and resolve the infection. In contrast, surgically splenectomized mice experience persistent waves of patent parasitemia interrupted briefly by periods of parasitologic crises. Transfer of spleen cells from immune donors, but not transfer of spleen cells from normal mice, into splenectomized mice enabled the recipients to resolve the infection similar to mice with intact spleens. B-cell depletion, but not T-cell depletion, of spleen cells prior to transfer abrogated the ability of splenectomized recipients to resolve the infection. Compared with mice with intact spleens, splenectomized mice exhibited a delayed antibody response whereas all groups of immune cell recipients had an accelerated antibody response. Nevertheless, splenectomized mice and recipients of B-cell-depleted cells failed to resolve infections, despite the development of high-titer antibodies late during the course of infection. Analysis of immunoglobulin G isotype responses showed a lower representation of immunoglobulin G2a in mice which failed to resolve infections. The latter mice had characteristic histopathologic changes in the liver. These observations indicate a unique role of the splenic microenvironment for the induction and development of an effective B-cell-dependent response against malarial parasites.
Yap
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GS
Centre for the Study of Host Resistance, Montreal General Hospital Research Institute, Quebec, Canada.
Stevenson
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MM
D000818:Animals; D000913:Antibodies, Protozoan / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000032:analysis; D016219:Immunotherapy, Adoptive; D008288:Malaria / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016788:Plasmodium chabaudi / Q000276:immunology*; D013154:Spleen / Q000502:physiology*
D000913:Antibodies, Protozoan; D007132:Immunoglobulin Isotypes