{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T19:06:20Z","timestamp":1775588780241,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010026","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000}}],"reference-count":119,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ghent University Global Campus core funding"},{"name":"Ghent University Global Campus core funding"},{"name":"UGent BOF grant 585","award":["BOF.STG.2018.0009.01\/01N01518"],"award-info":[{"award-number":["BOF.STG.2018.0009.01\/01N01518"]}]},{"name":"FWO grant","award":["G013518N"],"award-info":[{"award-number":["G013518N"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Salivarian trypanosomes are extracellular protozoan parasites causing infections in a wide range of mammalian hosts, with<jats:italic>Trypanosoma evansi<\/jats:italic>having the widest geographic distribution, reaching territories far outside Africa and occasionally even Europe. Besides causing the animal diseases,<jats:italic>T<\/jats:italic>.<jats:italic>evansi<\/jats:italic>can cause atypical Human Trypanosomosis. The success of this parasite is attributed to its capacity to evade and disable the mammalian defense response. To unravel the latter, we applied here for the first time a scRNA-seq analysis on splenocytes from trypanosome infected mice, at two time points during infection, i.e. just after control of the first parasitemia peak (day 14) and a late chronic time point during infection (day 42). This analysis was combined with flow cytometry and ELISA, revealing that<jats:italic>T<\/jats:italic>.<jats:italic>evansi<\/jats:italic>induces prompt activation of splenic IgM<jats:sup>+<\/jats:sup>CD1d<jats:sup>+<\/jats:sup>Marginal Zone and IgM<jats:sup>Int<\/jats:sup>IgD<jats:sup>+<\/jats:sup>Follicular B cells, coinciding with an increase in plasma IgG2c Ab levels. Despite the absence of follicles, a rapid accumulation of<jats:italic>Aicda<\/jats:italic><jats:sup>+<\/jats:sup>GC-like B cells followed first parasitemia peak clearance, accompanied by the occurrence of<jats:italic>Xbp1<\/jats:italic><jats:sup><jats:italic>+<\/jats:italic><\/jats:sup>expressing CD138<jats:sup>+<\/jats:sup>plasma B cells and<jats:italic>Tbx21<\/jats:italic><jats:sup>+<\/jats:sup>atypical CD11c<jats:sup>+<\/jats:sup>memory B cells. Ablation of immature CD93<jats:sup>+<\/jats:sup>bone marrow and<jats:italic>Vpreb3<\/jats:italic><jats:sup>+<\/jats:sup><jats:italic>Ly6d<\/jats:italic><jats:sup>+<\/jats:sup><jats:italic>Ighm<\/jats:italic><jats:sup>+<\/jats:sup>expressing transitional spleen B cells prevented mature peripheral B cell replenishment. Interestingly, AID<jats:sup>-\/-<\/jats:sup>mice that lack the capacity to mount anti-parasite IgG responses, exhibited a superior defense level against<jats:italic>T<\/jats:italic>.<jats:italic>evansi<\/jats:italic>infections. Here, elevated natural IgMs were able to exert<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro<\/jats:italic>trypanocidal activity. Hence, we conclude that in immune competent mice, trypanosomosis associated B cell activation and switched IgG production is rapidly induced by<jats:italic>T<\/jats:italic>.<jats:italic>evansi<\/jats:italic>, facilitating an escape from the detrimental natural IgM killing activity, and resulting in increased host susceptibility. This unique role of IgM and its anti-trypanosome activity are discussed in the context of the dilemma this causes for the future development of anti-trypanosome vaccines.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010026","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T18:41:17Z","timestamp":1636656077000},"page":"e1010026","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":36,"title":["Single-cell transcriptome profiling and the use of AID deficient mice reveal that B cell activation combined with antibody class switch recombination and somatic hypermutation do not benefit the control of experimental trypanosomosis"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1642-4700","authenticated-orcid":true,"given":"Hang Thi Thu","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4809-1816","authenticated-orcid":true,"given":"Robin B.","family":"Guevarra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3760-7968","authenticated-orcid":true,"given":"Stefan","family":"Magez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Radwanska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,11,11]]},"reference":[{"key":"ppat.1010026.ref001","first-page":"257","article-title":"Epidemiology of human African trypanosomiasis","volume":"6","author":"JR Franco","year":"2014","journal-title":"Clin Epidemiol"},{"key":"ppat.1010026.ref002","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.3389\/fimmu.2018.02253","article-title":"Salivarian Trypanosomosis: A Review of Parasites Involved, Their Global Distribution and Their Interaction With the Innate and Adaptive Mammalian Host Immune System","volume":"9","author":"M Radwanska","year":"2018","journal-title":"Front Immunol"},{"issue":"9","key":"ppat.1010026.ref003","doi-asserted-by":"crossref","first-page":"e2256","DOI":"10.1371\/journal.pntd.0002256","article-title":"Atypical human infections by animal trypanosomes","volume":"7","author":"P Truc","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"issue":"8","key":"ppat.1010026.ref004","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1093\/cid\/ciw052","article-title":"A clinical and epidemiological investigation of the first reported human infection with the zoonotic parasite Trypanosoma evansi in Southeast Asia","volume":"62","author":"N Van Vinh Chau","year":"2016","journal-title":"Clinical Infectious Diseases"},{"issue":"26","key":"ppat.1010026.ref005","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1056\/NEJMoa063265","article-title":"Human Trypanosoma evansi infection linked to a lack of apolipoprotein L-I","volume":"355","author":"B Vanhollebeke","year":"2006","journal-title":"N Engl J Med"},{"issue":"3\u20134","key":"ppat.1010026.ref006","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.vetpar.2014.05.004","article-title":"Control and eventual eradication of Trypanosoma evansi infection in dromedary camels after an episodic outbreak in mainland Spain: an example in a non-endemic area","volume":"204","author":"C Gutierrez","year":"2014","journal-title":"Vet Parasitol"},{"key":"ppat.1010026.ref007","doi-asserted-by":"crossref","first-page":"194176","DOI":"10.1155\/2013\/194176","article-title":"Trypanosoma evansi and surra: a review and perspectives on origin, history, distribution, taxonomy, morphology, hosts, and pathogenic effects","volume":"2013","author":"M Desquesnes","year":"2013","journal-title":"Biomed Res Int"},{"issue":"1","key":"ppat.1010026.ref008","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13071-019-3311-4","article-title":"Systematic review and meta-analysis on the global distribution, host range, and prevalence of Trypanosoma evansi","volume":"12","author":"WG Aregawi","year":"2019","journal-title":"Parasites & vectors"},{"issue":"12","key":"ppat.1010026.ref009","doi-asserted-by":"crossref","first-page":"e1800181","DOI":"10.1002\/bies.201800181","article-title":"Evolution of Antigenic Variation in African Trypanosomes: Variant Surface Glycoprotein Expression, Structure, and Function","volume":"40","author":"JD Bangs","year":"2018","journal-title":"Bioessays"},{"issue":"6","key":"ppat.1010026.ref010","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1042\/ETLS20170104","article-title":"Emerging challenges in understanding trypanosome antigenic variation","volume":"1","author":"R McCulloch","year":"2017","journal-title":"Emerg Top Life Sci"},{"issue":"3","key":"ppat.1010026.ref011","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.cell.2007.08.046","article-title":"Hydrodynamic flow-mediated protein sorting on the cell surface of trypanosomes","volume":"131","author":"M Engstler","year":"2007","journal-title":"Cell"},{"issue":"1","key":"ppat.1010026.ref012","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1128\/iai.52.1.223-229.1986","article-title":"Restriction of the alternative pathway of human complement by intact Trypanosoma brucei subsp. gambiense","volume":"52","author":"DV Devine","year":"1986","journal-title":"Infect Immun"},{"issue":"1\u20132","key":"ppat.1010026.ref013","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0165-2427(93)90121-J","article-title":"Immune lysis of Trypanosoma congolense: generation of a soluble covalent complex of variant surface glycoprotein and bovine complement component C3b","volume":"38","author":"EW Liu","year":"1993","journal-title":"Vet Immunol Immunopathol"},{"key":"ppat.1010026.ref014","doi-asserted-by":"crossref","first-page":"382","DOI":"10.3389\/fimmu.2020.00382","article-title":"Infections With Extracellular Trypanosomes Require Control by Efficient Innate Immune Mechanisms and Can Result in the Destruction of the Mammalian Humoral Immune System","volume":"11","author":"S Magez","year":"2020","journal-title":"Front Immunol"},{"issue":"5","key":"ppat.1010026.ref015","first-page":"817","article-title":"Experimental bovine trypanosomiasis. Changes in serum immunoglobulins, complement and complement components in infected animals","volume":"35","author":"K Nielsen","year":"1978","journal-title":"Immunology"},{"issue":"3","key":"ppat.1010026.ref016","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1128\/iai.27.3.832-836.1980","article-title":"Hemolytic complement and serum C3 levels in Zebu cattle infected with Trypanosoma congolense and Trypanosoma vivax and the effect of trypanocidal treatment","volume":"27","author":"FR Rurangirwa","year":"1980","journal-title":"Infect Immun"},{"issue":"6","key":"ppat.1010026.ref017","doi-asserted-by":"crossref","first-page":"e1002089","DOI":"10.1371\/journal.ppat.1002089","article-title":"T. brucei infection reduces B lymphopoiesis in bone marrow and truncates compensatory splenic lymphopoiesis through transitional B-cell apoptosis","volume":"7","author":"V Bockstal","year":"2011","journal-title":"PLoS Pathog"},{"issue":"7","key":"ppat.1010026.ref018","doi-asserted-by":"crossref","first-page":"e1005733","DOI":"10.1371\/journal.ppat.1005733","article-title":"Trypanosoma brucei Co-opts NK Cells to Kill Splenic B2 B Cells","volume":"12","author":"D Frenkel","year":"2016","journal-title":"PLoS Pathog"},{"issue":"5","key":"ppat.1010026.ref019","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/pim.12099","article-title":"Chronic Trypanosoma congolense infections in mice cause a sustained disruption of the B-cell homeostasis in the bone marrow and spleen","volume":"36","author":"E Obishakin","year":"2014","journal-title":"Parasite Immunol"},{"issue":"8","key":"ppat.1010026.ref020","article-title":"Trypanosoma vivax infections: pushing ahead with mouse models for the study of Nagana. II. Immunobiological dysfunctions","volume":"4","author":"MC Blom-Potar","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"issue":"5","key":"ppat.1010026.ref021","doi-asserted-by":"crossref","first-page":"e1000078","DOI":"10.1371\/journal.ppat.1000078","article-title":"Trypanosomiasis-induced B cell apoptosis results in loss of protective anti-parasite antibody responses and abolishment of vaccine-induced memory responses","volume":"4","author":"M Radwanska","year":"2008","journal-title":"PLoS Pathog"},{"key":"ppat.1010026.ref022","unstructured":"Magez S, Bockstal V, Brombacher F, Black S, Radwanska M, editors. Parasite-induced B-cell apoptosis results in loss of specific protective anti-trypanosome antibody responses, and abolishment of vaccine induced protective memory responses. 12th International congress of Parasitology (ICOPA); 6th Novel Approaches to the Control of Helminth Parasites of Liverstock conference; 2010: Medimond."},{"issue":"2\u20133","key":"ppat.1010026.ref023","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0304-4017(02)00363-1","article-title":"The effect of Trypanosoma evansi infection on pig performance and vaccination against classical swine fever","volume":"111","author":"WG Holland","year":"2003","journal-title":"Vet Parasitol"},{"issue":"4","key":"ppat.1010026.ref024","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s11250-009-9461-1","article-title":"Immune responses to haemorrhagic septicaemia (HS) vaccination in Trypanosoma evansi infected buffalo-calves","volume":"42","author":"LD Singla","year":"2010","journal-title":"Trop Anim Health Prod"},{"issue":"1","key":"ppat.1010026.ref025","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0021-9975(97)80067-9","article-title":"Effects of Trypanosoma evansi on the output of cells from a lymph node draining the site of Pasteurella haemolytica vaccine administration","volume":"117","author":"DN Onah","year":"1997","journal-title":"J Comp Pathol"},{"issue":"3","key":"ppat.1010026.ref026","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0304-4017(01)00534-9","article-title":"The influence of T. evansi infection on the immuno-responsiveness of experimentally infected water buffaloes","volume":"102","author":"WG Holland","year":"2001","journal-title":"Vet Parasitol"},{"issue":"8","key":"ppat.1010026.ref027","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1128\/JCM.00456-10","article-title":"Low specificities of HIV diagnostic tests caused by Trypanosoma brucei gambiense sleeping sickness","volume":"48","author":"V Lejon","year":"2010","journal-title":"J Clin Microbiol"},{"issue":"1","key":"ppat.1010026.ref028","first-page":"10","article-title":"Expression of the B cell repertoire and autoantibodies in human African trypanosomiasis","volume":"65","author":"G Kazyumba","year":"1986","journal-title":"Clin Exp Immunol"},{"issue":"3","key":"ppat.1010026.ref029","doi-asserted-by":"crossref","first-page":"e1003947","DOI":"10.1371\/journal.ppat.1003947","article-title":"Gambiense human african trypanosomiasis and immunological memory: effect on phenotypic lymphocyte profiles and humoral immunity","volume":"10","author":"V Lejon","year":"2014","journal-title":"PLoS Pathog"},{"issue":"10","key":"ppat.1010026.ref030","doi-asserted-by":"crossref","first-page":"e12664","DOI":"10.1111\/pim.12664","article-title":"Trypanosoma brucei brucei causes a rapid and persistent influx of neutrophils in the spleen of infected mice","volume":"41","author":"V Deleeuw","year":"2019","journal-title":"Parasite Immunol"},{"issue":"12","key":"ppat.1010026.ref031","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.3324\/haematol.2010.025767","article-title":"The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker for identifying c-MYC translocated lymphomas","volume":"95","author":"SJ Rodig","year":"2010","journal-title":"Haematologica"},{"issue":"5","key":"ppat.1010026.ref032","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.4049\/jimmunol.1600297","article-title":"Identification of Stage-Specific Surface Markers in Early B Cell Development Provides Novel Tools for Identification of Progenitor Populations","volume":"197","author":"CT Jensen","year":"2016","journal-title":"J Immunol"},{"issue":"1","key":"ppat.1010026.ref033","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.exppara.2006.11.010","article-title":"Protection of mice against homologous or heterologous infections with antiserum mixture to the predominant variable antigen type repertoire of Trypanosoma evansi YNB stock","volume":"116","author":"C Yang","year":"2007","journal-title":"Exp Parasitol"},{"key":"ppat.1010026.ref034","doi-asserted-by":"crossref","first-page":"582","DOI":"10.3389\/fimmu.2017.00582","article-title":"African Trypanosomes Undermine Humoral Responses and Vaccine Development: Link with Inflammatory Responses?","volume":"8","author":"B Stijlemans","year":"2017","journal-title":"Front Immunol"},{"issue":"10","key":"ppat.1010026.ref035","doi-asserted-by":"crossref","first-page":"5492","DOI":"10.4049\/jimmunol.151.10.5492","article-title":"Suppressor macrophages in African trypanosomiasis inhibit T cell proliferative responses by nitric oxide and prostaglandins","volume":"151","author":"KW Schleifer","year":"1993","journal-title":"J Immunol"},{"issue":"1\u20132","key":"ppat.1010026.ref036","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.cell.2018.10.041","article-title":"Oligopeptide Signaling through TbGPR89 Drives Trypanosome Quorum Sensing","volume":"176","author":"F Rojas","year":"2019","journal-title":"Cell"},{"issue":"5","key":"ppat.1010026.ref037","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/S1074-7613(01)00129-7","article-title":"Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens","volume":"14","author":"F Martin","year":"2001","journal-title":"Immunity"},{"issue":"2","key":"ppat.1010026.ref038","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/cmi.2012.63","article-title":"Regulatory functions of innate-like B cells","volume":"10","author":"X Zhang","year":"2013","journal-title":"Cell Mol Immunol"},{"issue":"1","key":"ppat.1010026.ref039","doi-asserted-by":"crossref","first-page":"518","DOI":"10.4049\/jimmunol.0900068","article-title":"Generation of protective T cell-independent antiviral antibody responses in SCID mice reconstituted with follicular or marginal zone B cells","volume":"183","author":"HM Guay","year":"2009","journal-title":"J Immunol"},{"key":"ppat.1010026.ref040","doi-asserted-by":"crossref","first-page":"11826","DOI":"10.1038\/ncomms11826","article-title":"Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection","volume":"7","author":"C Bohannon","year":"2016","journal-title":"Nat Commun"},{"issue":"8","key":"ppat.1010026.ref041","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1086\/521681","article-title":"Interleukin-12p70-dependent interferon- gamma production is crucial for resistance in African trypanosomiasis","volume":"196","author":"M Barkhuizen","year":"2007","journal-title":"J Infect Dis"},{"issue":"13","key":"ppat.1010026.ref042","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1084\/jem.20151620","article-title":"STAT1 regulates marginal zone B cell differentiation in response to inflammation and infection with blood-borne bacteria","volume":"213","author":"TT Chen","year":"2016","journal-title":"J Exp Med"},{"issue":"5545","key":"ppat.1010026.ref043","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1126\/science.1065500","article-title":"Defective antigen processing in GILT-free mice","volume":"294","author":"M Maric","year":"2001","journal-title":"Science"},{"issue":"10","key":"ppat.1010026.ref044","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.4049\/jimmunol.148.10.3275","article-title":"The IRG-47 gene is IFN-gamma induced in B cells and encodes a protein with GTP-binding motifs","volume":"148","author":"M Gilly","year":"1992","journal-title":"J Immunol"},{"issue":"7","key":"ppat.1010026.ref045","doi-asserted-by":"crossref","first-page":"3248","DOI":"10.4049\/jimmunol.1400531","article-title":"Putting J chain back on the map: how might its expression define plasma cell development?","volume":"193","author":"CD Castro","year":"2014","journal-title":"J Immunol"},{"issue":"1","key":"ppat.1010026.ref046","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1093\/intimm\/dxl122","article-title":"Extreme skewing of annexin II and S100A6 expression identified by proteomic analysis of peritoneal B-1 cells","volume":"19","author":"R Frances","year":"2007","journal-title":"Int Immunol"},{"issue":"1","key":"ppat.1010026.ref047","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/imm.12171","article-title":"Identification of co-expressed gene signatures in mouse B1, marginal zone and B2 B-cell populations","volume":"141","author":"NA Mabbott","year":"2014","journal-title":"Immunology"},{"key":"ppat.1010026.ref048","author":"K Hayakawa","journal-title":"Crucial Role of Increased Arid3a at the Pre-B and Immature B Cell Stages for B1a Cell Generation"},{"issue":"1","key":"ppat.1010026.ref049","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/nyas.12771","article-title":"FCRL regulation in innate-like B cells","volume":"1362","author":"RS Davis","year":"2015","journal-title":"Ann N Y Acad Sci"},{"issue":"3","key":"ppat.1010026.ref050","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/j.1365-3024.1998.00125.x","article-title":"Induction of CD4+ CD8+ double positive T cells and increase in CD5+ B cells in efferent lymph in sheep infected with Trypanosoma evansi","volume":"20","author":"DN ONAH","year":"1998","journal-title":"Parasite immunology"},{"issue":"2","key":"ppat.1010026.ref051","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1046\/j.1365-2567.1997.00330.x","article-title":"CD5+ B lymphocytes are the main source of antibodies reactive with non-parasite antigens in Trypanosoma congolense-infected cattle","volume":"92","author":"J Buza","year":"1997","journal-title":"Immunology"},{"issue":"3","key":"ppat.1010026.ref052","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.immuni.2004.06.019","article-title":"B1b lymphocytes confer T cell-independent long-lasting immunity","volume":"21","author":"KR Alugupalli","year":"2004","journal-title":"Immunity"},{"key":"ppat.1010026.ref053","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/nyas.12760","article-title":"B-1 lymphocytes in mice and nonhuman primates","volume":"1362","author":"KM Haas","year":"2015","journal-title":"Ann N Y Acad Sci"},{"key":"ppat.1010026.ref054","doi-asserted-by":"crossref","first-page":"535","DOI":"10.3389\/fimmu.2014.00535","article-title":"B1b cells recognize protective antigens after natural infection and vaccination","volume":"5","author":"AF Cunningham","year":"2014","journal-title":"Front Immunol"},{"issue":"5","key":"ppat.1010026.ref055","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1128\/IAI.01649-06","article-title":"CpG oligodeoxynucleotide treatment enhances innate resistance and acquired immunity to African trypanosomes","volume":"75","author":"TH Harris","year":"2007","journal-title":"Infect Immun"},{"issue":"4","key":"ppat.1010026.ref056","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.4049\/jimmunol.175.4.2501","article-title":"The induction of a type 1 immune response following a Trypanosoma brucei infection is MyD88 dependent","volume":"175","author":"MB Drennan","year":"2005","journal-title":"J Immunol"},{"issue":"11","key":"ppat.1010026.ref057","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.1182\/blood-2002-11-3569","article-title":"A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells","volume":"101","author":"NL Bernasconi","year":"2003","journal-title":"Blood"},{"issue":"5601","key":"ppat.1010026.ref058","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1126\/science.1076071","article-title":"Maintenance of serological memory by polyclonal activation of human memory B cells","volume":"298","author":"NL Bernasconi","year":"2002","journal-title":"Science"},{"issue":"12","key":"ppat.1010026.ref059","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1111\/pim.12387","article-title":"Prospects for vaccination against pathogenic African trypanosomes","volume":"38","author":"SJ Black","year":"2016","journal-title":"Parasite Immunol"},{"issue":"10\u201311","key":"ppat.1010026.ref060","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1365-3024.2005.00791.x","article-title":"Regulation of innate and acquired immunity in African trypanosomiasis","volume":"27","author":"JM Mansfield","year":"2005","journal-title":"Parasite Immunol"},{"issue":"6","key":"ppat.1010026.ref061","doi-asserted-by":"crossref","first-page":"e0127437","DOI":"10.1371\/journal.pone.0127437","article-title":"CpG-ODN Class C Mediated Immunostimulation in Rabbit Model of Trypanosoma evansi Infection","volume":"10","author":"P Kumar","year":"2015","journal-title":"PLoS 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Krzyzak","year":"2016","journal-title":"J Immunol"},{"issue":"12","key":"ppat.1010026.ref069","doi-asserted-by":"crossref","first-page":"6775","DOI":"10.4049\/jimmunol.161.12.6775","article-title":"Resistance to the African trypanosomes is IFN-\u03b3 dependent","volume":"161","author":"CJ Hertz","year":"1998","journal-title":"The Journal of Immunology"},{"issue":"9","key":"ppat.1010026.ref070","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/pim.12208","article-title":"IFN-gamma mediates early B-cell loss in experimental African trypanosomosis","volume":"37","author":"J Cnops","year":"2015","journal-title":"Parasite Immunol"},{"issue":"10","key":"ppat.1010026.ref071","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1111\/pim.12344","article-title":"Maintenance of B cells during chronic murine Trypanosoma brucei gambiense infection","volume":"38","author":"J Cnops","year":"2016","journal-title":"Parasite 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Wu","year":"2017","journal-title":"Front Immunol"},{"key":"ppat.1010026.ref075","doi-asserted-by":"crossref","first-page":"609","DOI":"10.3389\/fimmu.2016.00609","article-title":"Type-I Interferon Responses: From Friend to Foe in the Battle against Chronic Viral Infection","volume":"7","author":"A Murira","year":"2016","journal-title":"Front Immunol"},{"issue":"7","key":"ppat.1010026.ref076","doi-asserted-by":"crossref","first-page":"4908","DOI":"10.4049\/jimmunol.181.7.4908","article-title":"Type I IFNs play a role in early resistance, but subsequent susceptibility, to the African trypanosomes","volume":"181","author":"R Lopez","year":"2008","journal-title":"J Immunol"},{"issue":"2","key":"ppat.1010026.ref077","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1093\/infdis\/jir734","article-title":"Distinct Toll-like receptor signals regulate cerebral parasite load and interferon alpha\/beta and tumor necrosis factor alpha-dependent T-cell infiltration in the brains of 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Povlsen","year":"2012","journal-title":"Nat Cell Biol"},{"issue":"1517","key":"ppat.1010026.ref089","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1098\/rstb.2008.0223","article-title":"Somatic hypermutation of immunoglobulin genes: lessons from proliferating cell nuclear antigenK164R mutant mice","volume":"364","author":"P Langerak","year":"2009","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"ppat.1010026.ref090","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1146\/annurev-immunol-020711-075032","article-title":"Germinal centers","volume":"30","author":"GD Victora","year":"2012","journal-title":"Annu Rev Immunol"},{"key":"ppat.1010026.ref091","doi-asserted-by":"crossref","first-page":"e13722","DOI":"10.7554\/eLife.13722","article-title":"The cell proliferation antigen Ki-67 organises heterochromatin","volume":"5","author":"M Sobecki","year":"2016","journal-title":"Elife"},{"issue":"3","key":"ppat.1010026.ref092","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.3892\/ol.2016.4171","article-title":"High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma","volume":"11","author":"R Ma","year":"2016","journal-title":"Oncol Lett"},{"issue":"1","key":"ppat.1010026.ref093","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.immuni.2007.05.018","article-title":"Class switch recombination and somatic hypermutation in early mouse B cells are mediated by B cell and Toll-like receptors","volume":"27","author":"JH Han","year":"2007","journal-title":"Immunity"},{"issue":"1","key":"ppat.1010026.ref094","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/08916934.2014.993027","article-title":"B cell TLR1\/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to 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Silva-Barrios","year":"2019","journal-title":"Eur J Immunol"},{"issue":"6","key":"ppat.1010026.ref109","doi-asserted-by":"crossref","first-page":"e0178853","DOI":"10.1371\/journal.pone.0178853","article-title":"Early derivation of IgM memory cells and bone marrow plasmablasts","volume":"12","author":"AM Papillion","year":"2017","journal-title":"PLoS One"},{"issue":"12","key":"ppat.1010026.ref110","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1084\/jem.20021457","article-title":"Unmutated immunoglobulin M can protect mice from death by influenza virus infection","volume":"197","author":"Y Harada","year":"2003","journal-title":"J Exp Med"},{"issue":"12","key":"ppat.1010026.ref111","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1084\/jem.20031223","article-title":"A critical role for induced IgM in the protection against West Nile virus infection","volume":"198","author":"MS Diamond","year":"2003","journal-title":"J Exp 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