{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T21:34:31Z","timestamp":1793655271738,"version":"4.5.1"},"reference-count":46,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5447","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1999,12,10]]},"abstract":"<jats:p>\n                    Natural antibodies are often dismissed from immunological analysis as \u201cbackground,\u201d but they may play an important role in conferring immunity against infections. In antibody-free mice infected with various viruses or with\n                    <jats:italic>Listeria monocytogenes<\/jats:italic>\n                    , viral or bacterial titers in peripheral organs, including the kidney and brain, were 10 to 100 times greater than in antibody-competent mice (and enhanced their susceptibility to some infections), and titers in secondary lymphoid organs were 10 to 100 times lower than in antibody-competent mice. Thus, natural antibodies play a crucial role by preventing pathogen dissemination to vital organs and by improving immunogenicity through enhanced antigen-trapping in secondary lymphoid organs.\n                  <\/jats:p>","DOI":"10.1126\/science.286.5447.2156","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T05:37:20Z","timestamp":1027748240000},"page":"2156-2159","source":"Crossref","is-referenced-by-count":755,"title":["Control of Early Viral and Bacterial Distribution and Disease by Natural Antibodies"],"prefix":"10.1126","volume":"286","author":[{"given":"Adrian F.","family":"Ochsenbein","sequence":"first","affiliation":[{"name":"Institute for Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Fehr","sequence":"additional","affiliation":[{"name":"Institute for Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Lutz","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Immunobiology, Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Suter","sequence":"additional","affiliation":[{"name":"M. Suter, Institute for Virology, University of Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Brombacher","sequence":"additional","affiliation":[{"name":"F. Brombacher, Department of Immunology, Groote Schuur Hospital, University of Cape Town, 7925 Cape Town, South Africa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Hengartner","sequence":"additional","affiliation":[{"name":"Institute for Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf M.","family":"Zinkernagel","sequence":"additional","affiliation":[{"name":"Institute for Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","first-page":"154","volume":"12","author":"Avrameas S.","year":"1991","unstructured":"Avrameas S., Immunol. Today 12, 154 (1991).","journal-title":"Immunol. Today"},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0167-5699(93)90063-Q","volume":"14","author":"Herzenberg L. A.","year":"1993","unstructured":"Herzenberg L. A., Kantor A. B., Immunol. Today 14, 79 (1993).","journal-title":"Immunol. Today"},{"key":"e_1_3_1_4_2","unstructured":"G. S. Wilson and A. A. Miles in Principles of Bacteriology and Immunity (Williams and Wilkins Baltimore MD 1961) pp. 1223\u20131252;"},{"key":"e_1_3_1_4_3","first-page":"175","volume":"56","author":"Gobet R.","year":"1988","unstructured":"Gobet R., et al., Exp. Cell. Biol. 56, 175 (1988).","journal-title":"Exp. Cell. Biol."},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1146\/annurev.immunol.16.1.545","volume":"16","author":"Carroll M. C.","year":"1998","unstructured":"Carroll M. C., Annu. Rev. Immunol. 16, 545 (1998);","journal-title":"Annu. Rev. Immunol."},{"key":"e_1_3_1_5_3","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.4049\/jimmunol.152.4.1727","volume":"152","author":"Thornton B. P.","year":"1994","unstructured":"Thornton B. P., Vetvicka V., Ross G. D., J. Immunol. 152, 1727 (1994).","journal-title":"J. Immunol."},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1600-065X.1986.tb01161.x","volume":"94","author":"Cohen I. R.","year":"1986","unstructured":"Cohen I. R., Immunol. Rev 94, 5 (1986).","journal-title":"Immunol. Rev"},{"key":"e_1_3_1_7_2","doi-asserted-by":"crossref","unstructured":"R. R. Reid et al. J. Immunol. 159 970 (1997).","DOI":"10.4049\/jimmunol.159.2.970"},{"key":"e_1_3_1_8_2","doi-asserted-by":"crossref","unstructured":"D. E. Briles et al. J. Exp. Med. 153 694 (1981).","DOI":"10.1084\/jem.153.3.694"},{"key":"e_1_3_1_9_2","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1600-065X.1989.tb00027.x","volume":"110","author":"Coutinho A.","year":"1989","unstructured":"Coutinho A., Immunol. Rev. 110, 63 (1989).","journal-title":"Immunol. Rev."},{"key":"#cr-split#-e_1_3_1_10_2.1","doi-asserted-by":"crossref","unstructured":"R. R. Wagner The Rhabdoviruses (Plenum New York 1987)","DOI":"10.1007\/978-1-4684-7032-1"},{"key":"#cr-split#-e_1_3_1_10_2.2","unstructured":"B. Dietzschold et al. in Virology B. N. Fields D. M. Knipe A. M. Howley Eds. (Raven New York 1995) pp. 1137-1159."},{"key":"e_1_3_1_11_2","unstructured":"VSV-IND and VSV-NJ were supplied by D. Kolakovsky (University of Geneva Switzerland) and viral titers were analyzed by focus-forming assay. The LCMV-WE virus and the plaque-forming assay were described previously ["},{"key":"e_1_3_1_11_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0166-0934(91)90018-U","volume":"33","author":"Battegay M.","year":"1991","unstructured":"Battegay M., et al., J. Virol. Methods 33, 191 (1991);","journal-title":"J. Virol. Methods"},{"key":"e_1_3_1_11_4","unstructured":"]. Vacc-WR plaque-forming assays were performed on BSC40 cells. Listeria titers were assessed as described previously ["},{"key":"e_1_3_1_11_5","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1084\/jem.185.5.921","volume":"185","author":"Fehr T.","year":"1997","unstructured":"Fehr T., et al., J. Exp. Med. 185, 921 (1997)].","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_12_2","unstructured":"The VSV- and LCMV-specific ELISA and the VSV neutralization assay have been described previously ["},{"key":"e_1_3_1_12_3","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.1.145"},{"key":"e_1_3_1_12_4","unstructured":"]. The vacc-WR\u2013specific ELISA was performed similarly."},{"key":"e_1_3_1_13_2","unstructured":"Listeria (5 \u00d7 10 6 CFU) were incubated for 30 min with 50 \u03bcl of serum of na\u0131\u0308ve C67BL\/6 or \u03bcMT mice at different dilutions. Samples were stained with 2 \u03bcl of goat anti-mouse IgM b (PharMingen) for 30 min at 4\u00b0C and analyzed with a FACScan. In some samples 0.1 M \u03b1-methyl- d -mannoside was added to block unspecific binding to glycosid groups."},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","unstructured":"M. F. Bachmann et al Science 262 1448 (1993).","DOI":"10.1126\/science.8248784"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/350423a0"},{"key":"e_1_3_1_15_3","doi-asserted-by":"crossref","unstructured":"; P. Mombaerts et al. Cell 68 869 (1992).","DOI":"10.1016\/0022-3913(92)90227-2"},{"key":"e_1_3_1_16_2","doi-asserted-by":"crossref","unstructured":"C. Lutz et al. Nature 393 797 (1998).","DOI":"10.1038\/31716"},{"key":"#cr-split#-e_1_3_1_17_2.1","doi-asserted-by":"crossref","unstructured":"U. M\u00fcller et al . Science 264 1918 (1994)","DOI":"10.1126\/science.8009221"},{"key":"#cr-split#-e_1_3_1_17_2.2","doi-asserted-by":"crossref","unstructured":"U. Steinhoff et al. J. Virol. 69 2153 (1995).","DOI":"10.1128\/jvi.69.4.2153-2158.1995"},{"key":"e_1_3_1_18_2","doi-asserted-by":"crossref","unstructured":"M. A. Klein et al. Nature 390 687 (1997);","DOI":"10.1038\/37789"},{"key":"e_1_3_1_18_3","doi-asserted-by":"crossref","first-page":"9584","DOI":"10.1128\/JVI.73.11.9584-9588.1999","volume":"73","author":"Frigg R.","year":"1999","unstructured":"Frigg R., Klein M. A., Zinkernagel R. M., Aguzzi A., J. Virol. 73, 9584 (1999).","journal-title":"J. Virol."},{"key":"e_1_3_1_19_2","unstructured":"A. R. Thomsen et al. Int. Immunol. 9 1757 (1997). Thomsen et al. reconstituted \u03bcMT mice with sera containing VSV-specific IgM or IgG antibodies and with sera of unimmunized mice as a control. After challenge with 10 6 PFU of VSV only sera containing VSV induced specific antibodies but not normal serum-mediated protection. The dose used in these experiments was about 100 to 1000 times above LD 50 for \u03bcMT mice."},{"key":"e_1_3_1_20_2","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/eji.1830180221","volume":"18","author":"Vieira P.","year":"1988","unstructured":"Vieira P., Rajewsky K., Eur. J. Immunol. 18, 313 (1988).","journal-title":"Eur. J. Immunol."},{"key":"e_1_3_1_21_2","unstructured":"F. Fenner B. R. McAuslan C. A. Mims J. Sambrook D. O. White The Biology of Animal Viruses (Academic Press London 1974)."},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60197-2"},{"key":"e_1_3_1_22_3","doi-asserted-by":"crossref","first-page":"3074","DOI":"10.4049\/jimmunol.157.7.3074","volume":"157","author":"Thomsen A. R.","year":"1996","unstructured":"Thomsen A. R., Johansen J., Marker O., Christensen J. P., J. Immunol. 157, 3074 (1996).","journal-title":"J. Immunol."},{"key":"e_1_3_1_23_2","doi-asserted-by":"crossref","unstructured":"J. Rothe et al. Nature 364 798 (1993);","DOI":"10.1038\/364798a0"},{"key":"e_1_3_1_23_3","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev.iy.11.040193.001021","volume":"11","author":"Kaufmann S. H. E.","year":"1993","unstructured":"Kaufmann S. H. E., Annu. Rev. Immunol. 11, 129 (1993).","journal-title":"Annu. Rev. Immunol."},{"key":"e_1_3_1_24_2","doi-asserted-by":"crossref","first-page":"605","DOI":"10.4049\/jimmunol.101.3.605","volume":"101","author":"Frei P. C.","year":"1968","unstructured":"Frei P. C., Cruchaud S., Arnaud L., Vannotti A., J. Immunol. 101, 605 (1968);","journal-title":"J. Immunol."},{"key":"e_1_3_1_24_3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0065-2776(08)60296-5","volume":"16","author":"Weigle W. O.","year":"1973","unstructured":"Weigle W. O., Adv. Immunol. 16, 61 (1973).","journal-title":"Adv. Immunol."},{"key":"e_1_3_1_25_2","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1002\/eji.1830111006","volume":"11","author":"Lamers M. C.","year":"1981","unstructured":"Lamers M. C., De Groot E. R., Roos D., Eur. J. Immunol. 11, 764 (1981).","journal-title":"Eur. J. Immunol."},{"key":"#cr-split#-e_1_3_1_26_2.1","doi-asserted-by":"crossref","unstructured":"U. Karrer et al. J. Exp. Med. 185 2157 (1997)","DOI":"10.1084\/jem.185.12.2157"},{"key":"#cr-split#-e_1_3_1_26_2.2","doi-asserted-by":"crossref","unstructured":"A. F. Ochsenbein et al. Proc. Natl. Acad. Sci. U.S.A. 96 2233 (1999).","DOI":"10.1073\/pnas.96.5.2233"},{"key":"e_1_3_1_27_2","doi-asserted-by":"crossref","unstructured":"M.-A. Br\u00fcndler et al. Eur. J. Immunol. 26 2257 (1996).","DOI":"10.1002\/eji.1830260943"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5258.50"},{"key":"e_1_3_1_28_3","unstructured":"; M. R. Ehrenstein T. L. O\u2032Keefe"},{"key":"e_1_3_1_28_4","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1073\/pnas.95.17.10089","volume":"95","author":"Davies S. L.","year":"1998","unstructured":"Davies S. L., Neuberger M. S., Proc. Natl. Acad. Sci. U.S.A. 95, 10089 (1998) .","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_1_29_2","doi-asserted-by":"crossref","unstructured":"T. Fehr et al. Cell. Immunol. 168 184 (1996).","DOI":"10.1006\/cimm.1996.0065"},{"key":"e_1_3_1_30_2","unstructured":"We thank A. Macpherson for sera of germ-free mice and for reading the manuscript. Supported by the Swiss National Science Foundation (grant number 31-50900.97 to R.M.Z.) and the Kanton of Zurich."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.286.5447.2156","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T05:31:07Z","timestamp":1705123867000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.286.5447.2156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,12,10]]},"references-count":46,"journal-issue":{"issue":"5447","published-print":{"date-parts":[[1999,12,10]]}},"alternative-id":["10.1126\/science.286.5447.2156"],"URL":"https:\/\/doi.org\/10.1126\/science.286.5447.2156","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,12,10]]}}}