{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:01:37Z","timestamp":1792569697063,"version":"4.5.0"},"reference-count":36,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1998,12,21]]},"abstract":"<jats:p>To evaluate the role of natural immunoglobulin (Ig)M in the immediate response against microbial infection, we tested mutant mice that are deficient in secreted (s)IgM in an acute peritonitis model induced by cecal ligation and puncture (CLP). 20% of wild-type mice died within 32 h of CLP, whereas 70% of sIgM-deficient mice died within the same time period. The increased susceptibility was associated with a reduced level of tumor necrosis factor (TNF)-\u03b1, a decreased neutrophil recruitment and an increased bacterial load in the peritoneum, and elevated levels of endotoxin and proinflammatory cytokines in the circulation. Resistance to CLP by sIgM-deficient mice was restored by reconstitution with polyclonal IgM from normal mouse serum. Reconstitution with a monoclonal IgM specific to phosphatidylcholine, a conserved cell membrane component, has a modest effect but a monoclonal IgM specific to phosphocholine is not protective. These findings demonstrate a critical role of natural IgM in the immediate defense against severe bacterial infection.<\/jats:p>","DOI":"10.1084\/jem.188.12.2381","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"2381-2386","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":442,"title":["A Critical Role of Natural Immunoglobulin M in Immediate Defense Against Systemic Bacterial Infection"],"prefix":"10.1084","volume":"188","author":[{"given":"Marianne","family":"Boes","sequence":"first","affiliation":[{"name":"From the *Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; and the \u2021Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02135"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey P.","family":"Prodeus","sequence":"additional","affiliation":[{"name":"From the *Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; and the \u2021Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02135"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Schmidt","sequence":"additional","affiliation":[{"name":"From the *Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; and the \u2021Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02135"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Carroll","sequence":"additional","affiliation":[{"name":"From the *Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; and the \u2021Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02135"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhu","family":"Chen","sequence":"additional","affiliation":[{"name":"From the *Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; and the \u2021Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02135"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1998,12,21]]},"reference":[{"key":"2023072508093094000_B1","first-page":"202","article-title":"Autoimmunity: from physiology to pathology. Natural antibodies, mucosal immunity and development of B cell repertoire","volume":"38","author":"Tlaskalov\u00e1-Hogenov\u00e1","year":"1992","journal-title":"Folia Biol (Praha)"},{"key":"2023072508093094000_B2","first-page":"154","article-title":"Natural autoantibodies: from \u2018horor autotoxicus' to \u2018gnothi seauton.'","volume":"12","author":"Avrameas","year":"1991","journal-title":"Immunol Today"},{"key":"2023072508093094000_B3","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/0952-7915(95)80053-0","article-title":"Natural autoantibodies","volume":"7","author":"Coutinho","year":"1995","journal-title":"Curr Opin Immunol"},{"key":"2023072508093094000_B4","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1146\/annurev.iy.11.040193.002441","article-title":"Origin of murine B cell lineages","volume":"11","author":"Kantor","year":"1993","journal-title":"Annu Rev Immunol"},{"key":"2023072508093094000_B5","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0065-2776(08)60512-X","article-title":"CD5 B cells, a fetal B cell lineage","volume":"55","author":"Hardy","year":"1994","journal-title":"Adv Immunol"},{"key":"2023072508093094000_B6"},{"key":"2023072508093094000_B7","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/311727a0","article-title":"Preferential utilization of the most JH-proximal VHgene segments in pre-B-cell lines","volume":"311","author":"Yancopoulos","year":"1984","journal-title":"Nature"},{"key":"2023072508093094000_B8","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1084\/jem.172.5.1377","article-title":"Lack of N regions in fetal and neonatal mouse immunoglobulin V-D-J junctional sequences","volume":"172","author":"Feeney","year":"1990","journal-title":"J Exp Med"},{"key":"2023072508093094000_B9","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1002\/j.1460-2075.1990.tb07382.x","article-title":"Sequence homologies, N sequence insertion and JH gene utilization in VHDJHjoining: implications for the joining mechanism and the ontogenetic timing of Ly1 B cell and B-CLL progenitor generation","volume":"9","author":"Gu","year":"1990","journal-title":"EMBO (Eur Mol Biol Organ) J"},{"key":"2023072508093094000_B10"},{"key":"2023072508093094000_B11","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1084\/jem.168.2.687","article-title":"Normal mouse peritoneum contains a large population of Ly1+(CD5) B cells that recognize phosphatidyl choline","volume":"168","author":"Mercolino","year":"1988","journal-title":"J Exp Med"},{"key":"2023072508093094000_B12","doi-asserted-by":"crossref","first-page":"3642","DOI":"10.4049\/jimmunol.142.10.3643","article-title":"A single VH gene is utilized predominantly in anti-BrMRBC hybridomas derived from purified Ly-1 B cells: definition of the VH11 family","volume":"142","author":"Hardy","year":"1989","journal-title":"J Immunol"},{"key":"2023072508093094000_B13","doi-asserted-by":"crossref","first-page":"4776","DOI":"10.4049\/jimmunol.160.10.4776","article-title":"Enhanced B-1 cell development, but impaired IgG antibody responses in mice deficient in secreted IgM","volume":"160","author":"Boes","year":"1998","journal-title":"J Immunol"},{"key":"2023072508093094000_B14","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-4804(80)90037-2","article-title":"Sepsis and septic shock\u2014a review of laboratory models and a proposal","volume":"29","author":"Wichterman","year":"1980","journal-title":"J Surg Res"},{"key":"2023072508093094000_B15","doi-asserted-by":"crossref","first-page":"3762","DOI":"10.4049\/jimmunol.145.11.3762","article-title":"Requirement of endogenous tumor necrosis factor\/ cachectin for recovery from experimental peritonitis","volume":"145","author":"Echtenacher","year":"1990","journal-title":"J Immunol"},{"key":"2023072508093094000_B16","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.4049\/jimmunol.141.11.4012","article-title":"Genetics of the phosphocholine-specific antibody response to Streptococcus pneumoniae.","volume":"141","author":"Claflin","year":"1988","journal-title":"J Immunol"},{"key":"2023072508093094000_B17","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/36586","article-title":"Impaired mast cell-dependent natural immunity in complement C3-deficient mice","volume":"390","author":"Prodeus","year":"1997","journal-title":"Nature"},{"key":"2023072508093094000_B18","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/381075a0","article-title":"Critical protective role of mast cells in a model of acute septic peritonitis","volume":"381","author":"Echtenacher","year":"1996","journal-title":"Nature"},{"key":"2023072508093094000_B19","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/381077a0","article-title":"Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-\u03b1","volume":"381","author":"Malaviya","year":"1996","journal-title":"Nature"},{"key":"2023072508093094000_B20","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/330662a0","article-title":"Anti-cachectin\/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia","volume":"330","author":"Tracey","year":"1987","journal-title":"Nature"},{"key":"2023072508093094000_B21","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0065-2776(08)60340-5","article-title":"The classical complement pathway: activation and regulation of the first complement component","volume":"37","author":"Cooper","year":"1985","journal-title":"Adv Immunol"},{"key":"2023072508093094000_B22","doi-asserted-by":"crossref","first-page":"970","DOI":"10.4049\/jimmunol.159.2.970","article-title":"Endotoxin shock in antibody-deficient mice","volume":"159","author":"Reid","year":"1997","journal-title":"J Immunol"},{"key":"2023072508093094000_B23","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/0167-5699(90)90173-7","article-title":"Biological and clinical aspects of interleukin 6","volume":"11","author":"Hirano","year":"1990","journal-title":"Immunol Today"},{"key":"2023072508093094000_B24","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0167-5699(94)90137-6","article-title":"The acute phase response","volume":"15","author":"Baumann","year":"1994","journal-title":"Immunol Today"},{"key":"2023072508093094000_B25","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0167-5699(94)90138-4","article-title":"The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein","volume":"15","author":"Steel","year":"1994","journal-title":"Immunol Today"},{"key":"2023072508093094000_B26","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1042\/bj1100573","article-title":"Pneumococcal C-substance, a ribitol teichoic acid containing choline phosphate","volume":"110","author":"Brundish","year":"1968","journal-title":"Biochem J"},{"key":"2023072508093094000_B27","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1084\/jem.153.3.694","article-title":"Antiphosphocholine antibodies found in normal mouse serum are protective against intravenous infection with type 3 Streptococcus pneumoniae.","volume":"153","author":"Briles","year":"1981","journal-title":"J Exp Med"},{"key":"2023072508093094000_B28","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1128\/iai.36.1.184-188.1982","article-title":"Protection of mice from infection with Streptococcus pneumoniaeby anti-phosphocholine antibody","volume":"36","author":"Yother","year":"1981","journal-title":"Infect Immun"},{"key":"2023072508093094000_B29","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1056\/NEJM197002122820701","article-title":"Increased susceptibility to infection associated with abnormalities of complement-mediated functions and of the third complement component (C3)","volume":"282","author":"Alper","year":"1970","journal-title":"N Engl J Med"},{"key":"2023072508093094000_B30","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1084\/jem.179.2.569","article-title":"The third component of complement protects against Escherichia coliendotoxin-induced shock and multiple organ failure","volume":"179","author":"Quezado","year":"1994","journal-title":"J Exp Med"},{"key":"2023072508093094000_B31","doi-asserted-by":"crossref","first-page":"11490","DOI":"10.1073\/pnas.92.25.11490","article-title":"Studies of group B streptococcal infection in mice deficient in complement component C3 or C4 demonstrate an essential role for complement in both innate and acquired immunity","volume":"92","author":"Wessels","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072508093094000_B32","doi-asserted-by":"crossref","first-page":"3986","DOI":"10.1128\/iai.60.10.3986-3993.1992","article-title":"Prevention of C3 deposition by capsular polysaccharide is a virulence mechanism of type III group B Streptococci","volume":"60","author":"Marques","year":"1992","journal-title":"Infect Immun"},{"key":"2023072508093094000_B33","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1146\/annurev.me.38.020187.002221","article-title":"Endotoxins and disease mechanisms","volume":"38","author":"Morrison","year":"1987","journal-title":"Annu Rev Med"},{"key":"2023072508093094000_B34","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/0140-6736(91)91452-Z","article-title":"Septic shock: pathogenesis","volume":"338","author":"Glauser","year":"1991","journal-title":"Lancet"},{"key":"2023072508093094000_B35","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.4049\/jimmunol.128.3.1278","article-title":"Capsular sialic acid prevents activation of the alternative complement pathway by type III, group B streptococci","volume":"128","author":"Edwards","year":"1982","journal-title":"J Immunol"},{"key":"2023072508093094000_B36","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1172\/JCI114858","article-title":"Immunogenicity in animals of a polysaccharide\u2013protein conjugate vaccine against type III group B Streptococcus.","volume":"86","author":"Wessels","year":"1990","journal-title":"J Clin Invest"}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/188\/12\/2381\/1689618\/98-1697.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/188\/12\/2381\/1689618\/98-1697.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T09:14:49Z","timestamp":1690276489000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/188\/12\/2381\/7680\/A-Critical-Role-of-Natural-Immunoglobulin-M-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,12,21]]},"references-count":36,"journal-issue":{"issue":"12","published-print":{"date-parts":[[1998,12,21]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.188.12.2381","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,12,21]]}}}