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Surprisingly, infection of immunodeficient recombination-activating gene 2-deficient (RAG2<jats:sup>\u2212\/\u2212<\/jats:sup>) mice with 5 \u00d7 10<jats:sup>2<\/jats:sup>PFU of LCMV-WE causes about 80-fold-lower LCMV titers in the spleen on day 4 postinfection compared with C57BL\/6 control mice. This could not be attributed to NK cell activity, since common gamma-chain-deficient RAG2<jats:sup>\u2212\/\u2212<\/jats:sup>mice lacking NK cells show low LCMV titers comparable to those for RAG2<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Furthermore, the reduced early LCMV production in spleens could not be explained by an enhanced gamma interferon production in RAG2<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Analysis of mutant mice exhibiting various defects in the splenic microarchitecture, including (i) tumor necrosis factor alpha-negative (TNF-\u03b1<jats:sup>\u2212\/\u2212<\/jats:sup>), lymphotoxin alpha-negative (LT\u03b1<jats:sup>\u2212\/\u2212<\/jats:sup>), B-cell-deficient \u03bcMT mice, (ii) immunoglobulin M-negative mice, and (iii) RAG<jats:sup>\u2212\/\u2212<\/jats:sup>mice reconstituted with wild-type versus TNF-\u03b1<jats:sup>\u2212\/\u2212<\/jats:sup>LT\u03b1<jats:sup>\u2212\/\u2212<\/jats:sup>B cells, revealed a clear correlation between an intact splenic marginal zone, rapid early replication of LCMV in the spleen, and efficient CTL induction. These results suggest that by the preferential infection of the highly organized splenic microarchitecture, LCMV seems to successfully exploit one of the key elements in the chain of the adaptive immune system. Not only does the early tropism of LCMV for the splenic marginal zone trigger a potent immune response, but at the same time the marginal zone may also become a target of early CTL-mediated immunopathology that impairs immune responsiveness.<\/jats:p>","DOI":"10.1128\/jvi.76.5.2375-2383.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:56:57Z","timestamp":1027763817000},"page":"2375-2383","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":47,"title":["Role of an Intact Splenic Microarchitecture in Early Lymphocytic Choriomeningitis Virus Production"],"prefix":"10.1128","volume":"76","author":[{"given":"Stefan","family":"Mu\u0308ller","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Bern, CH-3010 Bern"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Hunziker","sequence":"additional","affiliation":[{"name":"Institute for Experimental Immunology, University of Zurich, CH-8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Enzler","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Bern, CH-3010 Bern"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Bu\u0308hler-Jungo","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Bern, CH-3010 Bern"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Di Santo","sequence":"additional","affiliation":[{"name":"Institut Pasteur, F-75724 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf M.","family":"Zinkernagel","sequence":"additional","affiliation":[{"name":"Institute for Experimental Immunology, University of Zurich, CH-8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Bern, CH-3010 Bern"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830220720"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","unstructured":"Battegay M. 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