{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:03:19Z","timestamp":1788883399537,"version":"build-2803163510"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007059","name":"Northwestern University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007059","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>T cell-based therapies have been widely explored for the treatment of cancer and chronic infection, but B cell-based therapies have remained largely unexplored. To study the effect of B cell therapy, we adoptively transferred virus-specific B cells into mice that were chronically infected with lymphocytic choriomeningitis virus (LCMV). Adoptive transfer of virus-specific B cells resulted in increase in antibody titers and reduction of viral loads. Importantly, the efficacy of B cell therapy was partly dependent on antibody effector functions, and was improved by co-transferring virus-specific CD4 T cells. These findings provide a proof-of-concept that adoptive B cell therapy can be effective for the treatment of chronic infections, but provision of virus-specific CD4 T cells may be critical for optimal virus neutralization.<\/jats:p>","DOI":"10.3389\/fimmu.2022.908707","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T13:32:17Z","timestamp":1658842337000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Adoptive B cell therapy for chronic viral infection"],"prefix":"10.3389","volume":"13","author":[{"given":"Young Rock","family":"Chung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanushree","family":"Dangi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Palacio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Penaloza-MacMaster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aah6817","article-title":"Interferon-driven deletion of antiviral b cells at the onset of chronic infection","volume":"1","author":"Fallet","year":"2016","journal-title":"Sci Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aah6789","article-title":"Inflammatory monocytes hinder antiviral b cell responses","volume":"1","author":"Sammicheli","year":"2016","journal-title":"Sci Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aah3565","article-title":"Type I interferon suppresses virus-specific b cell responses by modulating CD8(+) T cell differentiation","volume":"1","author":"Moseman","year":"2016","journal-title":"Sci Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.01.005","article-title":"Suppression of fcgamma-Receptor-Mediated antibody effector function during persistent viral infection","volume":"42","author":"Yamada","year":"2015","journal-title":"Immunity"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.04.005","article-title":"Regulatory b cells: Origin, phenotype, and function","volume":"42","author":"Rosser","year":"2015","journal-title":"Immunity"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nri3469","article-title":"How b cells capture, process and present antigens: A crucial role for cell polarity","volume":"13","author":"Yuseff","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B7","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.133.2.855","article-title":"The blockade of fc receptor-mediated clearance of immune complexes In vivo by a monoclonal antibody (2.4G2) directed against fc receptors on murine leukocytes","volume":"133","author":"Kurlander","year":"1984","journal-title":"J Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/s41590-021-01077-y","article-title":"Targeting BMI-1 in b cells restores effective humoral immune responses and controls chronic viral infection","volume":"23","author":"Di Pietro","year":"2022","journal-title":"Nat Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nm1670","article-title":"Extralymphatic virus sanctuaries as a consequence of potent T-cell activation","volume":"13","author":"Recher","year":"2007","journal-title":"Nat Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083317","article-title":"Defective CD8 T cell memory following acute infection without CD4 T cell help","volume":"300","author":"Sun","year":"2003","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.12.8056-8063.1994","article-title":"CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection","volume":"68","author":"Matloubian","year":"1994","journal-title":"J Virol"},{"key":"B12","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1118450109","article-title":"Antigen-specific CD4 T-cell help rescues exhausted CD8 T cells during chronic viral infection","volume":"108","author":"Aubert","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa2148","article-title":"Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection","volume":"347","author":"Penaloza-MacMaster","year":"2015","journal-title":"Science"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.42995","article-title":"Reprogramming the antigen specificity of b cells using genome-editing technologies","volume":"8","author":"Voss","year":"2019","journal-title":"Elife"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46023","article-title":"Depletion of CD4(+) T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques","volume":"121","author":"Ortiz","year":"2011","journal-title":"J Clin Invest"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.08.018","article-title":"CD8(+) lymphocytes are required for maintaining viral suppression in SIV-infected macaques treated with short-term antiretroviral therapy","volume":"45","author":"Cartwright","year":"2016","journal-title":"Immunity"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5403.857","article-title":"Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes","volume":"283","author":"Schmitz","year":"1999","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/ncomms1100","article-title":"B-cell depletion reveals a role for antibodies in the control of chronic HIV-1 infection","volume":"1","author":"Huang","year":"2010","journal-title":"Nat Commun"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.13.6874","article-title":"A critical role for neutralizing-Antibody-Producing b cells, CD4(+) T cells, and interferons in persistent and acute infections of mice with lymphocytic choriomeningitis virus: Implications for adoptive immunotherapy of virus carriers","volume":"94","author":"Planz","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20132577","article-title":"Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection","volume":"211","author":"Penaloza-MacMaster","year":"2014","journal-title":"J Exp Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007583","article-title":"TLR4 signaling improves PD-1 blockade therapy during chronic viral infection","volume":"15","author":"Wang","year":"2019","journal-title":"PloS Pathog"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2108157118","article-title":"Vaccine-elicited CD4 T cells prevent the deletion of antiviral b cells in chronic infection","volume":"118","author":"Narr","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.08.065","article-title":"Overcoming CD4 Th1 cell fate restrictions to sustain antiviral CD8 T cells and control persistent virus infection","volume":"16","author":"Snell","year":"2016","journal-title":"Cell Rep"},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1401662111","article-title":"Type I interferon suppresses De novo virus-specific CD4 Th1 immunity during an established persistent viral infection","volume":"111","author":"Osokine","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aam8686","article-title":"Sustained T follicular helper cell response is essential for control of chronic viral infection","volume":"2","author":"Greczmiel","year":"2017","journal-title":"Sci Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1126\/science.1208421","article-title":"Late interleukin-6 escalates T follicular helper cell responses and controls a chronic viral infection","volume":"334","author":"Harker","year":"2011","journal-title":"Science"},{"key":"B27","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2135542100","article-title":"Antiviral immune responses in gene-targeted mice expressing the immunoglobulin heavy chain of virus-neutralizing antibodies","volume":"100","author":"Hangartner","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"B28","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1002\/(SICI)1521-4141(199801)28:01<390::AID-IMMU390>3.0.CO;2-O","article-title":"Virus-specific MHC-class II-restricted TCR-transgenic mice: Effects on humoral and cellular immune responses after viral infection","volume":"28","author":"Oxenius","year":"1998","journal-title":"Eur J Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12771","article-title":"Regulation of CD4 T cells and their effects on immunopathological inflammation following viral infection","volume":"152","author":"Bhattacharyya","year":"2017","journal-title":"Immunology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/cpim.99","article-title":"Interrogating adaptive immunity using LCMV","author":"Dangi","year":"2020","journal-title":"Curr Protoc Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abi8635","article-title":"Fractionating a COVID-19 Ad5-vectored vaccine improves virus-specific immunity","volume":"6","author":"Sanchez","year":"2021","journal-title":"Sci Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI151969","article-title":"Cross-protective immunity following coronavirus vaccination and coronavirus infection","volume":"131","author":"Dangi","year":"2021","journal-title":"J Clin Invest"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109664:109664","article-title":"Combining spike- and nucleocapsid-based vaccines improves distal control of SARS-CoV-2","author":"Dangi","year":"2021","journal-title":"Cell Rep"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20191220","article-title":"Early type I IFN blockade improves the efficacy of viral vaccines","volume":"217","author":"Palacio","year":"2020","journal-title":"J Exp Med"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.vaccine.2016.11.063","article-title":"Development of novel replication-defective lymphocytic choriomeningitis virus vectors expressing SIV antigens","volume":"35","author":"Penaloza MacMaster","year":"2017","journal-title":"Vaccine"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.908707\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,12]],"date-time":"2023-02-12T16:15:51Z","timestamp":1676218551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.908707\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,26]]},"references-count":35,"alternative-id":["10.3389\/fimmu.2022.908707"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.908707","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,26]]},"article-number":"908707"}}