{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:51:58Z","timestamp":1792709518147,"version":"4.5.0"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2011,5,26]],"date-time":"2011-05-26T00:00:00Z","timestamp":1306368000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1002066","type":"journal-article","created":{"date-parts":[[2011,5,26]],"date-time":"2011-05-26T16:55:51Z","timestamp":1306428951000},"page":"e1002066","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":75,"title":["Lymphoadenopathy during Lyme Borreliosis Is Caused by Spirochete Migration-Induced Specific B Cell Activation"],"prefix":"10.1371","volume":"7","author":[{"given":"Stefan S.","family":"Tunev","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine J.","family":"Hastey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emir","family":"Hodzic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunlian","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W.","family":"Barthold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Baumgarth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2011,5,26]]},"reference":[{"key":"ref1","first-page":"1","article-title":"Surveillance for Lyme disease - United States, 1992\u20132006.","volume":"57","author":"RM Bacon","year":"2008","journal-title":"MMWR Surveill Summ"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1098\/rstb.2001.0893","article-title":"The shifting landscap of tick-borne zoonoses: tick-borne encephalitiis and Lyme borreliosis in Europe.","volume":"356","author":"SE Randolph","year":"2001","journal-title":"Phil Trans R Soc Lond"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"725","DOI":"10.7326\/0003-4819-107-5-725","article-title":"The clinical evolution of Lyme arthritis.","volume":"107","author":"AC Steere","year":"1987","journal-title":"Ann Intern Med"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1056\/NEJM198908313210906","article-title":"Lyme disease.","volume":"321","author":"AC Steere","year":"1989","journal-title":"N Engl J Med"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM200107123450207","article-title":"Lyme disease.","volume":"345","author":"AC Steere","year":"2001","journal-title":"N Eng J Med"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcpa.2004.11.006","article-title":"Histopathological studies of experimental Lyme disease in dogs.","volume":"133","author":"BA Summers","year":"2005","journal-title":"J Comp Path"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1749-6632.1988.tb31839.x","article-title":"Clinical pathologic correlations of Lyme disease by stage.","volume":"539","author":"PH Duray","year":"1988","journal-title":"Ann N Y Acad Sci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"76","DOI":"10.7326\/0003-4819-99-1-76","article-title":"The early clinical manifestations of Lyme disease.","volume":"99","author":"AC Steere","year":"1983","journal-title":"Ann Intern Med"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1093\/infdis\/165.3.471","article-title":"Nonspecific proliferative responses of murine lymphocytes to <italic>Borrelia burgdorferi<\/italic> antigens.","volume":"165","author":"MS deSouza","year":"1992","journal-title":"J Infect Dis"},{"key":"ref10","first-page":"389","article-title":"A 14,000 MW lipoprotein and a glycolipid-like structure of <italic>Borrelia burgdorferi<\/italic> induce proliferation and immunoglobulin production in mouse B cells at high frequencey.","volume":"82","author":"N Honarvar","year":"1994","journal-title":"Immunol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"3843","DOI":"10.1128\/IAI.61.9.3843-3853.1993","article-title":"<italic>Borrelia burgdorferi<\/italic> outer surface lipoproteins OspA and OspB possess B-cell mitogenic and cytokine-stimulatory properties.","volume":"61","author":"Y Ma","year":"1993","journal-title":"Infect Immun"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1128\/IAI.60.2.455-464.1992","article-title":"Demonstration of a B-lymphocyte mitogen produced by the Lyme disease pathogen, <italic>Borrelia burgdorferi<\/italic>.","volume":"60","author":"R Schoenfeld","year":"1992","journal-title":"Infect Immun"},{"key":"ref13","first-page":"648","article-title":"In vivo and in vitro evidence of B cell hyperactivity during Lyme disease.","volume":"15","author":"LH Sigal","year":"1988","journal-title":"J Rheumatol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1128\/IAI.62.2.520-528.1994","article-title":"Normal human B lymphocytes and mononuclear cells respond to the mitogenic and cytokine-stimulatory activities of <italic>Borrelia burgdorferi<\/italic> and its lipoprotein OspA.","volume":"62","author":"KF Tai","year":"1994","journal-title":"Infect Immun"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1128\/IAI.61.4.1460-1467.1993","article-title":"Specific and nonspecific responses of murine B-cells to membrane blebs of <italic>Borrelia burgdorferi<\/italic>.","volume":"61","author":"WM Whitmire","year":"1993","journal-title":"Infect Immun"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1128\/IAI.60.8.3033-3041.1992","article-title":"Evidence for lymphocyte<italic>-<\/italic>B mitogen activity in <italic>Borrelia burgdorferi<\/italic>-infected mice.","volume":"60","author":"LM Yang","year":"1992","journal-title":"Infect Immun"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1038\/nm.2036","article-title":"Salmonella disrupts lymph node architecture by TLR4-mediated suppression of homeostatic chemokines.","volume":"15","author":"AL St John","year":"2009","journal-title":"Nat Med"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.4049\/jimmunol.177.3.1755","article-title":"Mast cells have a pivotal role in TNF-independent lymph node hypertrophy and the mobilization of Langerhans cells in response to bacterial peptidoglycan.","volume":"177","author":"DM Jawdat","year":"2006","journal-title":"J Immunol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/ni1005","article-title":"Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection.","volume":"4","author":"JB McLachlan","year":"2003","journal-title":"Nat Immunol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"3090","DOI":"10.1128\/JCM.31.12.3090-3095.1993","article-title":"Serodiagnosis in early Lyme disease.","volume":"31","author":"ME Aguero-Rosenfeld","year":"1993","journal-title":"J Clin Microbiol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/JCM.34.1.1-9.1996","article-title":"Evolution of the serologic response to <italic>Borrelia burgdorferi<\/italic> in treated patients with culture-confirmed erythema migrans.","volume":"34","author":"ME AgueroRosenfeld","year":"1996","journal-title":"J Clin Microbiol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1093\/infdis\/167.2.392","article-title":"Western blotting in the serodiagnosis of early Lyme disease.","volume":"167","author":"F Dressler","year":"1993","journal-title":"J Infect Dis"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1086\/322669","article-title":"Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10-20 years after active disease.","volume":"33","author":"RA Kalish","year":"2001","journal-title":"Clin Infect Dis"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1172\/JCI21681","article-title":"The emergence of Lyme disease.","volume":"113","author":"AC Steere","year":"2004","journal-title":"J Clin Invest"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.2460\/javma.1995.207.11.1435","article-title":"Serologic response of naturally exposed or vaccinated dogs to <italic>Borrelia burgdorferi<\/italic>, the agent of Lyme borreliosis.","volume":"207","author":"SW Barthold","year":"1995","journal-title":"J Am Vet Med Assoc"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1086\/516166","article-title":"Protective and arthritis-resolving activity in serum from mice infected with <italic>Borrelia burgdorferi<\/italic>.","volume":"25","author":"SW Barthold","year":"1997","journal-title":"Clin Infect Dis"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1128\/IAI.63.6.2255-2261.1995","article-title":"Circumvention of outer surface protein A immunity by host-adapted <italic>Borrelia burgdorferi<\/italic>.","volume":"63","author":"SW Barthold","year":"1995","journal-title":"Infect Immun"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1093\/infdis\/169.3.568","article-title":"Sera from patients with chronic Lyme disease protect mice from Lyme borreliosis.","volume":"169","author":"E Fikrig","year":"1994","journal-title":"J Infect Dis"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"5190","DOI":"10.1128\/IAI.68.9.5190-5197.2000","article-title":"T-cell-independent responses to <italic>Borrelia burgdorferi<\/italic> are critical for protective immunity and resolution of Lyme disease.","volume":"68","author":"MD McKisic","year":"2000","journal-title":"Infect Immun"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1128\/IAI.61.11.4696-4702.1993","article-title":"Passive immunizing activity of sera from mice infected with <italic>Borrelia burgdorferi<\/italic>.","volume":"61","author":"SW Barthold","year":"1993","journal-title":"Infect Immun"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S1074-7613(00)80596-8","article-title":"Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function.","volume":"9","author":"O Adachi","year":"1998","journal-title":"Immunity"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1128\/IAI.73.6.3313-3321.2005","article-title":"Immunoglobulin-regulated expression of <italic>Borrelia burgdorferi<\/italic> outer surface protein A <italic>in vivo.<\/italic>","volume":"73","author":"E Hodzic","year":"2005","journal-title":"Infect Immun"},{"key":"ref33","first-page":"521","article-title":"Isolation and cultivation of Lyme disease spirochetes.","volume":"57","author":"AG Barbour","year":"1984","journal-title":"Yale J Biol Med"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"3382","DOI":"10.1128\/IAI.70.7.3382-3388.2002","article-title":"<italic>Borrelia burgdorferi<\/italic> population kinetics and selected gene expression at the host-vector interface.","volume":"70","author":"E Hodzic","year":"2002","journal-title":"Infect Immun"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/cyto.a.20252","article-title":"Evaluation of intranuclear BrdU detection procedures for use in multicolor flow cytometry.","volume":"69","author":"K Rothaeusler","year":"2006","journal-title":"Cytometry A"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.1128\/IAI.66.6.2827-2835.1998","article-title":"Humoral immunity to <italic>Borrelia burgdorferi<\/italic> N40 decorin binding proteins during infection of laboratory mice.","volume":"66","author":"S Feng","year":"1998","journal-title":"Infect Immun"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"7661","DOI":"10.4049\/jimmunol.0803783","article-title":"B7-1\/2 (CD80\/CD86) direct signaling to B cells enhances IgG secretion.","volume":"183","author":"FC Rau","year":"2009","journal-title":"J Immunol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/infdis\/162.1.133","article-title":"Lyme borreliosis in selected strains and ages of laboratory mice.","volume":"162","author":"SW Barthold","year":"1990","journal-title":"J Infect Dis"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1172\/JCI119169","article-title":"Arthropod- and host-specific gene expression by <italic>Borrelia burgdorferi<\/italic>.","volume":"99","author":"AM deSilva","year":"1997","journal-title":"J Clin Invest"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4049\/jimmunol.157.1.1","article-title":"Protective antibodies in murine Lyme disease arise independently of CD40 ligand.","volume":"157","author":"E Fikrig","year":"1996","journal-title":"J Immunol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"4817","DOI":"10.1128\/IAI.00469-06","article-title":"Antibody-mediated disease remission in the mouse model of Lyme borreliosis.","volume":"74","author":"SW Barthold","year":"2006","journal-title":"Infect Immun"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1128\/IAI.72.6.3195-3203.2004","article-title":"Myeloid differentiation antigen 88 deficiency impairs pathogen clearance but does not alter inflammation in Borrelia burgdorferi-infected mice.","volume":"72","author":"N Liu","year":"2004","journal-title":"Infect Immun"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1034\/j.1600-065X.2003.00058.x","article-title":"Extrafollicular antibody responses.","volume":"194","author":"IC MacLennan","year":"2003","journal-title":"Immunol Rev"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/ni.1900","article-title":"Control systems and decision making for antibody production.","volume":"11","author":"CC Goodnow","year":"2010","journal-title":"Nat Immunol"},{"key":"ref45","article-title":"Lyme borreliosis in B cell- and ab T cell-deficient mice: distinct roles for specific immunity in disease regression.","volume":"25","author":"LK Bockenstedt","year":"1997","journal-title":"Clin Infect Dis"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1128\/IAI.71.6.3419-3428.2003","article-title":"Antigenic composition of Borrelia burgdorferi during infection of SCID mice.","volume":"71","author":"TR Crother","year":"2003","journal-title":"Infect Immun"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"7211","DOI":"10.1128\/IAI.71.12.7211-7214.2003","article-title":"Immunogenicity of Borrelia burgdorferi arthritis-related protein.","volume":"71","author":"S Feng","year":"2003","journal-title":"Infect Immun"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"5759","DOI":"10.1128\/IAI.72.10.5759-5767.2004","article-title":"Borrelia burgdorferi changes its surface antigenic expression in response to host immune responses.","volume":"72","author":"FT Liang","year":"2004","journal-title":"Infect Immun"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1128\/JCM.38.1.382-388.2000","article-title":"Temporal changes in outer surface proteins A and C of the Lyme disease-associated spirochete, Borrelia burgdorferi, during the chain of infection in ticks and mice.","volume":"38","author":"TG Schwan","year":"2000","journal-title":"J Clin Microbiol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"4269","DOI":"10.1073\/pnas.92.10.4269","article-title":"<italic>Borrelia burgdorferi<\/italic> genes selectively expressed in the infected host.","volume":"92","author":"K Suk","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"5379","DOI":"10.1128\/IAI.66.11.5379-5387.1998","article-title":"DbpA, but not OspA, is expressed by Borrelia burgdorferi during spirochemia and is a target for protective antibodies.","volume":"66","author":"DR Cassatt","year":"1998","journal-title":"Infect Immun"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1084\/jem.20011870","article-title":"An immune evasion mechanism for spirochetal persistence in Lyme borreliosis.","volume":"195","author":"FT Liang","year":"2002","journal-title":"J Exp Med"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/j.1574-6968.1994.tb06917.x","article-title":"Nucleotide sequence and analysis of the gene in Borrelia burgdorferi encoding the immunogenic P39 antigen.","volume":"119","author":"WJ Simpson","year":"1994","journal-title":"F E M S Microbiol Lett"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"4169","DOI":"10.1128\/IAI.68.7.4169-4173.2000","article-title":"Lyme arthritis resolution with antiserum to a 37-kilodalton <italic>Borrelia burgdorferi<\/italic> protein.","volume":"68","author":"S Feng","year":"2000","journal-title":"Infect Immun"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1128\/IAI.66.5.2143-2153.1998","article-title":"Active and passive immunity against <italic>Borrelia burgdorferi<\/italic> decorin binding protein A (DbpA) protects against infection.","volume":"66","author":"MS Hanson","year":"1998","journal-title":"Infect Immun"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1084\/jem.20070962","article-title":"Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis.","volume":"205","author":"U Pal","year":"2008","journal-title":"J Exp Med"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1128\/IAI.62.5.1920-1926.1994","article-title":"Protection of C3H\/HeN mice from challenge with <italic>Borrelia burgdorferi<\/italic> through active immunization with OspA, OspB, or OspC, but not with OspD or the 83-kilodalton antigen.","volume":"62","author":"WS Probert","year":"1994","journal-title":"Infect Immun"},{"key":"ref58","first-page":"57","article-title":"Serum-mediated resolution of Lyme arthritis in mice.","volume":"74","author":"SW Barthold","year":"1996","journal-title":"Lab Invest"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.tim.2007.06.003","article-title":"Hidden in plain sight: Borrelia burgdorferi and the extracellular matrix.","volume":"15","author":"FC Cabello","year":"2007","journal-title":"Trends Microbiol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1128\/IAI.00422-07","article-title":"Marginal zone B-cell depletion impairs murine host defense against Borrelia burgdorferi infection.","volume":"75","author":"AA Belperron","year":"2007","journal-title":"Infect Immun"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"4493","DOI":"10.1128\/IAI.61.10.4493-4497.1993","article-title":"Variant responses of mice to Borrelia burgdorferi depending on the site of intradermal inoculation.","volume":"61","author":"MS de Souza","year":"1993","journal-title":"Infect Immun"},{"key":"ref62","first-page":"345","article-title":"Murine Lyme borreliosis: route of inoculation determines immune response and infectivity.","volume":"4","author":"AR Pachner","year":"1993","journal-title":"Regional Immunol"}],"container-title":["PLoS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1002066","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,7]],"date-time":"2024-04-07T01:31:18Z","timestamp":1712453478000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1002066"}},"subtitle":[],"editor":[{"given":"Jenifer","family":"Coburn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2011,5,26]]},"references-count":62,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2011,5,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1002066","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5,26]]}}}