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Despite tremendous efforts and resources spent worldwide trying to explore antiviral drugs, there is still no effective clinical treatment for COVID-19 to date. Approximately 15% of COVID-19 cases progress to pneumonia, and patients with severe pneumonia may die from acute respiratory distress syndrome (ARDS). It is believed that pulmonary fibrosis from SARS-CoV-2 infection further leads to ARDS, often resulting in irreversible impairment of lung function. If the mechanisms by which SARS-CoV-2 infection primarily causes an immune response or immune cell infiltration can be identified, it may be possible to mitigate excessive immune responses by modulating the infiltration and activation of specific targets, thereby reducing or preventing severe lung damage. However, the extent to which immune cell subsets are significantly altered in the lung tissues of COVID-19 patients remains to be elucidated.<\/jats:p><jats:p>This study applied the CIBERSORT-X method to comprehensively evaluate the transcriptional estimated immune infiltration landscape in the lung tissues of COVID-19 patients and further compare it with the lung tissues of patients with idiopathic pulmonary fibrosis (IPF). We found a variety of immune cell subtypes in the COVID-19 group, especially na\u00efve B cells were highly infiltrated. Comparison of functional transcriptomic analyses revealed that non-differentiated na\u00efve B cells may be the main cause of the over-active humoral immune response. Using several publicly available single-cell RNA sequencing data to validate the genetic differences in B-cell populations, it was found that the B-cells collected from COVID-19 patients were inclined towards na\u00efve B-cells, whereas those collected from IPF patients were inclined towards memory B-cells. Further differentiation of B cells between COVID-19 mild and severe patients showed that B cells from severe patients tended to be antibody-secreting cells, and gene expression showed that B cells from severe patients were similar to DN2 B cells that trigger extrafollicular response. Moreover, a higher percentage of B-cell infiltration seems associated with poorer clinical outcome. Finally, a comparison of several specific COVID-19 cases treated with targeted B-cell therapy suggests that appropriate suppression of na\u00efve B cells might potentially be a novel strategy to alleviate the severe symptoms of COVID-19.<\/jats:p>","DOI":"10.1371\/journal.pone.0242900","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T18:45:58Z","timestamp":1606934758000},"page":"e0242900","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["In silico immune infiltration profiling combined with functional enrichment analysis reveals a potential role for na\u00efve B cells as a trigger for severe immune responses in the lungs of COVID-19 patients"],"prefix":"10.1371","volume":"15","author":[{"given":"Yi-Ying","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Huei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hsien","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Chen","family":"Yen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsing-Fan","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Liang","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1827-6924","authenticated-orcid":true,"given":"Yi-Lin","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,2]]},"reference":[{"issue":"8","key":"pone.0242900.ref001","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A Novel Coronavirus from Patients with Pneumonia in China, 2019","volume":"382","author":"N. Zhu","year":"2020","journal-title":"N Engl J Med"},{"issue":"13","key":"pone.0242900.ref002","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1056\/NEJMoa2001316","article-title":"Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia","volume":"382","author":"Q. Li","year":"2020","journal-title":"N Engl J Med"},{"issue":"4","key":"pone.0242900.ref003","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.jiph.2020.02.033","article-title":"The outbreak of Coronavirus Disease 2019 (COVID-19)-An emerging global health threat","volume":"13","author":"S. Arshad Ali","year":"2020","journal-title":"J Infect Public Health"},{"issue":"5","key":"pone.0242900.ref004","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/d41573-020-00073-5","article-title":"The COVID-19 vaccine development landscape","volume":"19","author":"T. 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Klopfenstein","year":"2020","journal-title":"Clin Res Hepatol Gastroenterol"},{"key":"pone.0242900.ref008","article-title":"Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study","author":"T. Chen","year":"2020","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"7","key":"pone.0242900.ref009","article-title":"Loss of smell or taste as the only symptom of COVID-19","volume":"140","author":"J. Hjelmesaeth","year":"2020","journal-title":"Tidsskr Nor Laegeforen"},{"issue":"18","key":"pone.0242900.ref010","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical Characteristics of Coronavirus Disease 2019 in China","volume":"382","author":"W.J. Guan","year":"2020","journal-title":"N Engl J Med"},{"key":"pone.0242900.ref011","article-title":"Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore","author":"B.E. Young","year":"2020","journal-title":"JAMA"},{"issue":"10223","key":"pone.0242900.ref012","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"C. Huang","year":"2020","journal-title":"Lancet"},{"key":"pone.0242900.ref013","article-title":"Abnormal pulmonary function in COVID-19 patients at time of hospital discharge","author":"X. Mo","year":"2020","journal-title":"Eur Respir J"},{"key":"pone.0242900.ref014","article-title":"Lung function testing in the COVID-19 endemic","author":"J.H. Hull","year":"2020","journal-title":"Lancet Respir Med"},{"key":"pone.0242900.ref015","article-title":"Pulmonary fibrosis secondary to COVID-19: a call to arms?","author":"P. Spagnolo","year":"2020","journal-title":"Lancet Respir Med"},{"key":"pone.0242900.ref016","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1146\/annurev-pathol-011110-130158","article-title":"The acute respiratory distress syndrome: pathogenesis and treatment","volume":"6","author":"M.A. Matthay","year":"2011","journal-title":"Annu Rev Pathol"},{"issue":"8","key":"pone.0242900.ref017","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1172\/JCI60331","article-title":"The acute respiratory distress syndrome","volume":"122","author":"M.A. Matthay","year":"2012","journal-title":"J Clin Invest"},{"issue":"5","key":"pone.0242900.ref018","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1165\/rcmb.2008-0348TR","article-title":"Transepithelial migration of neutrophils: mechanisms and implications for acute lung injury","volume":"40","author":"R.L. 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Liao","year":"2020","journal-title":"Nat Med"},{"issue":"5","key":"pone.0242900.ref023","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"A.M. Newman","year":"2015","journal-title":"Nat Methods"},{"key":"pone.0242900.ref024","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/978-1-4939-7493-1_12","article-title":"Profiling Tumor Infiltrating Immune Cells with CIBERSORT","volume":"1711","author":"B. Chen","year":"2018","journal-title":"Methods Mol Biol"},{"issue":"7","key":"pone.0242900.ref025","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41587-019-0114-2","article-title":"Determining cell type abundance and expression from bulk tissues with digital cytometry","volume":"37","author":"A.M. Newman","year":"2019","journal-title":"Nat Biotechnol"},{"issue":"1","key":"pone.0242900.ref026","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1136\/thoraxjnl-2013-204596","article-title":"Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis","volume":"70","author":"D.J. DePianto","year":"2015","journal-title":"Thorax"},{"issue":"22","key":"pone.0242900.ref027","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.131597","article-title":"Transcriptional regulatory model of fibrosis progression in the human lung","volume":"4","author":"J.E. McDonough","year":"2019","journal-title":"JCI Insight"},{"issue":"8","key":"pone.0242900.ref028","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/s41587-020-0602-4","article-title":"COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis","volume":"38","author":"R.L. Chua","year":"2020","journal-title":"Nat Biotechnol"},{"issue":"2","key":"pone.0242900.ref029","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.02441-2018","article-title":"Proliferating SPP1\/MERTK-expressing macrophages in idiopathic pulmonary fibrosis","volume":"54","author":"C. Morse","year":"2019","journal-title":"Eur Respir J"},{"issue":"43","key":"pone.0242900.ref030","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"A. Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"pone.0242900.ref031","doi-asserted-by":"crossref","first-page":"e13984","DOI":"10.1371\/journal.pone.0013984","article-title":"Enrichment map: a network-based method for gene-set enrichment visualization and interpretation","volume":"5","author":"D. Merico","year":"2010","journal-title":"PLoS One"},{"key":"pone.0242900.ref032","article-title":"Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy","author":"P.M. George","year":"2020","journal-title":"Lancet Respir Med"},{"issue":"14","key":"pone.0242900.ref033","doi-asserted-by":"crossref","first-page":"i436","DOI":"10.1093\/bioinformatics\/btz363","article-title":"Comprehensive evaluation of transcriptome-based cell-type quantification methods for immuno-oncology","volume":"35","author":"G. Sturm","year":"2019","journal-title":"Bioinformatics"},{"issue":"1","key":"pone.0242900.ref034","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s12967-019-1964-6","article-title":"Identification and validation of an immune cell infiltrating score predicting survival in patients with lung adenocarcinoma","volume":"17","author":"X. Yang","year":"2019","journal-title":"J Transl Med"},{"issue":"1","key":"pone.0242900.ref035","doi-asserted-by":"crossref","first-page":"6220","DOI":"10.1038\/s41598-018-24437-5","article-title":"Deviations of the immune cell landscape between healthy liver and hepatocellular carcinoma","volume":"8","author":"N. Rohr-Udilova","year":"2018","journal-title":"Sci Rep"},{"key":"pone.0242900.ref036","unstructured":"https:\/\/software.broadinstitute.org\/morpheus\/"},{"issue":"2","key":"pone.0242900.ref037","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.virol.2007.07.015","article-title":"Human CD4(+) memory T-lymphocyte responses to SARS coronavirus infection","volume":"368","author":"D.H. Libraty","year":"2007","journal-title":"Virology"},{"issue":"6","key":"pone.0242900.ref038","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/s41423-020-0447-2","article-title":"High-dimensional immune profiling by mass cytometry revealed immunosuppression and dysfunction of immunity in COVID-19 patients","volume":"17","author":"W. Wang","year":"2020","journal-title":"Cell Mol Immunol"},{"issue":"5","key":"pone.0242900.ref039","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.4049\/jimmunol.1203476","article-title":"Plasma B lymphocyte stimulator and B cell differentiation in idiopathic pulmonary fibrosis patients","volume":"191","author":"J. Xue","year":"2013","journal-title":"J Immunol"},{"issue":"1","key":"pone.0242900.ref040","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1186\/s12931-019-1195-7","article-title":"Enhanced Bruton\u2019s tyrosine kinase in B-cells and autoreactive IgA in patients with idiopathic pulmonary fibrosis","volume":"20","author":"P. Heukels","year":"2019","journal-title":"Respir Res"},{"issue":"6","key":"pone.0242900.ref041","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.4049\/jimmunol.180.6.3655","article-title":"Cutting edge: the dependence of plasma cells and independence of memory B cells on BAFF and APRIL","volume":"180","author":"M.J. Benson","year":"2008","journal-title":"J Immunol"},{"key":"pone.0242900.ref042","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1146\/annurev-immunol-041015-055605","article-title":"Follicular Helper T Cells","volume":"34","author":"C.G. Vinuesa","year":"2016","journal-title":"Annu Rev Immunol"},{"issue":"1","key":"pone.0242900.ref043","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1186\/s12931-019-1216-6","article-title":"Aberrant populations of circulating T follicular helper cells and regulatory B cells underlying idiopathic pulmonary fibrosis","volume":"20","author":"Y. Asai","year":"2019","journal-title":"Respir Res"},{"key":"pone.0242900.ref044","article-title":"B cell clonal expansion and convergent antibody responses to SARS-CoV-2","author":"Sandra C. A. Nielsen","year":"2020","journal-title":"Infectious Diseases"},{"issue":"4","key":"pone.0242900.ref045","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.molmed.2016.02.004","article-title":"Pulmonary Macrophages: A New Therapeutic Pathway in Fibrosing Lung Disease?","volume":"22","author":"A.J. Byrne","year":"2016","journal-title":"Trends Mol Med"},{"issue":"4","key":"pone.0242900.ref046","article-title":"Blood monocyte counts as a potential prognostic marker for idiopathic pulmonary fibrosis: analysis from the Australian IPF registry","volume":"55","author":"A.K.Y. Teoh","year":"2020","journal-title":"Eur Respir J"},{"issue":"4","key":"pone.0242900.ref047","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.immuni.2013.04.004","article-title":"Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes","volume":"38","author":"D. Hashimoto","year":"2013","journal-title":"Immunity"},{"issue":"10","key":"pone.0242900.ref048","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1084\/jem.20131199","article-title":"Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF","volume":"210","author":"M. Guilliams","year":"2013","journal-title":"J Exp Med"},{"issue":"3","key":"pone.0242900.ref049","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.immuni.2016.02.015","article-title":"Macrophages in Tissue Repair, Regeneration, and Fibrosis","volume":"44","author":"T.A. Wynn","year":"2016","journal-title":"Immunity"},{"key":"pone.0242900.ref050","article-title":"Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study","author":"M. Luca Carsana","year":"2020","journal-title":"The Lancet Infectious Diseases"},{"issue":"1","key":"pone.0242900.ref051","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1097\/ALN.0000000000000264","article-title":"Mechanical ventilation-associated lung fibrosis in acute respiratory distress syndrome: a significant contributor to poor outcome","volume":"121","author":"N.E. Cabrera-Benitez","year":"2014","journal-title":"Anesthesiology"},{"key":"pone.0242900.ref052","article-title":"Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals","author":"L. Ni","year":"2020","journal-title":"Immunity"},{"key":"pone.0242900.ref053","article-title":"Antibody responses to SARS-CoV-2 in patients with COVID-19","author":"Q.X. Long","year":"2020","journal-title":"Nat Med"},{"issue":"Database issue","key":"pone.0242900.ref054","doi-asserted-by":"crossref","first-page":"D674","DOI":"10.1093\/nar\/gkn653","article-title":"PID: the Pathway Interaction Database","volume":"37","author":"C.F. Schaefer","year":"2009","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"pone.0242900.ref055","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.smim.2009.05.010","article-title":"The role of CD40 and CD154\/CD40L in dendritic cells","volume":"21","author":"D.Y. Ma","year":"2009","journal-title":"Semin Immunol"},{"issue":"5580","key":"pone.0242900.ref056","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.1071632","article-title":"Integrin-mediated long-term B cell retention in the splenic marginal zone","volume":"297","author":"T.T. Lu","year":"2002","journal-title":"Science"},{"issue":"5","key":"pone.0242900.ref057","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/S1074-7613(04)00105-0","article-title":"LFA-1\/ICAM-1 interaction lowers the threshold of B cell activation by facilitating B cell adhesion and synapse formation","volume":"20","author":"Y.R. Carrasco","year":"2004","journal-title":"Immunity"},{"issue":"7","key":"pone.0242900.ref058","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/ni.3175","article-title":"Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus","volume":"16","author":"C.M. Tipton","year":"2015","journal-title":"Nat Immunol"},{"issue":"10","key":"pone.0242900.ref059","doi-asserted-by":"crossref","first-page":"6624","DOI":"10.4049\/jimmunol.178.10.6624","article-title":"A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus","volume":"178","author":"C. Wei","year":"2007","journal-title":"J Immunol"},{"issue":"8","key":"pone.0242900.ref060","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1084\/jem.20072682","article-title":"Discriminating gene expression profiles of memory B cell subpopulations","volume":"205","author":"G.R. Ehrhardt","year":"2008","journal-title":"J Exp Med"},{"issue":"3","key":"pone.0242900.ref061","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/nri3795","article-title":"The generation of antibody-secreting plasma cells","volume":"15","author":"S.L. Nutt","year":"2015","journal-title":"Nat Rev Immunol"},{"issue":"12","key":"pone.0242900.ref062","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1038\/ni.3287","article-title":"Regulation of bifurcating B cell trajectories by mutual antagonism between transcription factors IRF4 and IRF8","volume":"16","author":"H. Xu","year":"2015","journal-title":"Nat Immunol"},{"issue":"4","key":"pone.0242900.ref063","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.immuni.2018.08.015","article-title":"Distinct Effector B Cells Induced by Unregulated Toll-like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus","volume":"49","author":"S.A. Jenks","year":"2018","journal-title":"Immunity"},{"issue":"1","key":"pone.0242900.ref064","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/imr.12741","article-title":"Extrafollicular responses in humans and SLE","volume":"288","author":"S.A. Jenks","year":"2019","journal-title":"Immunol Rev"},{"issue":"2","key":"pone.0242900.ref065","doi-asserted-by":"crossref","first-page":"351","DOI":"10.4049\/jimmunol.1801208","article-title":"The Multifaceted B Cell Response to Influenza Virus","volume":"202","author":"J.H. Lam","year":"2019","journal-title":"J Immunol"},{"issue":"10","key":"pone.0242900.ref066","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1084\/jem.20011866","article-title":"The B cell antigen receptor controls integrin activity through Btk and PLCgamma2","volume":"198","author":"M. Spaargaren","year":"2003","journal-title":"J Exp Med"},{"issue":"7","key":"pone.0242900.ref067","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.4049\/jimmunol.1002090","article-title":"Protective B cell responses to flu\u2014no fluke!","volume":"186","author":"E.E. Waffarn","year":"2011","journal-title":"J Immunol"},{"key":"pone.0242900.ref068","doi-asserted-by":"crossref","first-page":"8991","DOI":"10.1038\/ncomms9991","article-title":"Infection-induced type I interferons activate CD11b on B-1 cells for subsequent lymph node accumulation","volume":"6","author":"E.E. Waffarn","year":"2015","journal-title":"Nat Commun"},{"issue":"13","key":"pone.0242900.ref069","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.1084\/jem.20080979","article-title":"Dual role for B-1a cells in immunity to influenza virus infection","volume":"205","author":"Y.S. Choi","year":"2008","journal-title":"J Exp Med"},{"issue":"11","key":"pone.0242900.ref070","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nri3070","article-title":"Monocyte recruitment during infection and inflammation","volume":"11","author":"C. Shi","year":"2011","journal-title":"Nat Rev Immunol"},{"issue":"2","key":"pone.0242900.ref071","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.molimm.2014.06.010","article-title":"How antibodies use complement to regulate antibody responses","volume":"61","author":"A. Sorman","year":"2014","journal-title":"Mol Immunol"},{"key":"pone.0242900.ref072","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fimmu.2016.00099","article-title":"Emerging Functions of Natural IgM and Its Fc Receptor FCMR in Immune Homeostasis","volume":"7","author":"H. Wang","year":"2016","journal-title":"Front Immunol"},{"issue":"5","key":"pone.0242900.ref073","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.4049\/jimmunol.161.5.2223","article-title":"Critical role of IL-12 in dendritic cell-induced differentiation of naive B lymphocytes","volume":"161","author":"B. Dubois","year":"1998","journal-title":"J Immunol"},{"issue":"4","key":"pone.0242900.ref074","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/cyto.a.23737","article-title":"Human Germinal Center B Cells Differ from Naive and Memory B Cells in CD40 Expression and CD40L-Induced Signaling Response","volume":"95","author":"K. Huse","year":"2019","journal-title":"Cytometry A"},{"key":"pone.0242900.ref075","article-title":"Critically ill SARS-CoV-2 patients display lupus-like hallmarks of extrafollicular","author":"Matthew Woodruff","year":"2020","journal-title":"B cell activation"},{"key":"pone.0242900.ref076","article-title":"A possible role for B cells in COVID-19? Lesson from patients with agammaglobulinemia","author":"I. Quinti","year":"2020","journal-title":"J Allergy Clin Immunol"},{"issue":"1","key":"pone.0242900.ref077","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1006\/clim.2001.5197","article-title":"Absence of memory B cells in patients with common variable immunodeficiency","volume":"103","author":"K. Agematsu","year":"2002","journal-title":"Clin Immunol"},{"key":"pone.0242900.ref078","first-page":"D917","article-title":"Bruton tyrosine kinase (BTK) in X-linked agammaglobulinemia (XLA)","volume":"5","author":"M. Vihinen","year":"2000","journal-title":"Front Biosci"},{"issue":"6","key":"pone.0242900.ref079","doi-asserted-by":"crossref","first-page":"957","DOI":"10.2217\/fon.14.51","article-title":"Ibrutinib: a first in class covalent inhibitor of Bruton\u2019s tyrosine kinase","volume":"10","author":"M.S. Davids","year":"2014","journal-title":"Future Oncol"},{"issue":"Spec Feature","key":"pone.0242900.ref080","first-page":"89","article-title":"Imbruvica (Ibrutinib): First Drug Approved for the Treatment of Patients with Waldenstrom\u2019s Macroglobulinemia","volume":"9","author":"L.A. Raedler","year":"2016","journal-title":"Am Health Drug Benefits"},{"issue":"8","key":"pone.0242900.ref081","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1158\/1078-0432.CCR-18-1286","article-title":"Ibrutinib Therapy Releases Leukemic Surface IgM from Antigen Drive in Chronic Lymphocytic Leukemia Patients","volume":"25","author":"S. Drennan","year":"2019","journal-title":"Clin Cancer Res"},{"issue":"21","key":"pone.0242900.ref082","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1182\/blood.2020006288","article-title":"The BTK inhibitor ibrutinib may protect against pulmonary injury in COVID-19-infected patients","volume":"135","author":"S.P. Treon","year":"2020","journal-title":"Blood"},{"issue":"2","key":"pone.0242900.ref083","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/WNF.0b013e3181cbf825","article-title":"Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis","volume":"33","author":"J. Chun","year":"2010","journal-title":"Clin Neuropharmacol"},{"key":"pone.0242900.ref084","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.matbio.2018.01.006","article-title":"Sphingolipid signaling in renal fibrosis","volume":"68\u201369","author":"A. Huwiler","year":"2018","journal-title":"Matrix Biol"},{"issue":"4","key":"pone.0242900.ref085","doi-asserted-by":"crossref","DOI":"10.1212\/NXI.0000000000000753","article-title":"COVID-19 infection in a patient with multiple sclerosis treated with fingolimod","volume":"7","author":"M. Barzegar","year":"2020","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"22","key":"pone.0242900.ref086","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.2174\/138161206777947731","article-title":"LFA-1 as a key regulator of immune function: approaches toward the development of LFA-1-based therapeutics","volume":"12","author":"P.A. Giblin","year":"2006","journal-title":"Curr Pharm Des"},{"issue":"4","key":"pone.0242900.ref087","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.4049\/jimmunol.1700495","article-title":"Not Just an Adhesion Molecule: LFA-1 Contact Tunes the T Lymphocyte Program","volume":"199","author":"N.K. Verma","year":"2017","journal-title":"J Immunol"},{"issue":"11","key":"pone.0242900.ref088","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1007\/s00705-015-2579-8","article-title":"Beyond RGD: virus interactions with integrins","volume":"160","author":"H.A. Hussein","year":"2015","journal-title":"Arch Virol"},{"key":"pone.0242900.ref089","doi-asserted-by":"crossref","first-page":"102165","DOI":"10.1016\/j.msard.2020.102165","article-title":"COVID-19 occurring during Natalizumab treatment: a case report in a patient with extended interval dosing approach","volume":"41","author":"G. Borriello","year":"2020","journal-title":"Mult Scler Relat Disord"},{"issue":"5","key":"pone.0242900.ref090","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1159\/000302687","article-title":"Effects of natalizumab on circulating B cells, T regulatory cells and natural killer cells","volume":"63","author":"N. Putzki","year":"2010","journal-title":"Eur Neurol"},{"issue":"6","key":"pone.0242900.ref091","doi-asserted-by":"crossref","first-page":"e292","DOI":"10.1212\/NXI.0000000000000292","article-title":"Natalizumab treatment leads to an increase in circulating CXCR3-expressing B cells","volume":"3","author":"M. Saraste","year":"2016","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"pone.0242900.ref092","first-page":"e13502","article-title":"Dupilumab and COVID-19: What should we expect?","author":"C. Patruno","year":"2020","journal-title":"Dermatol Ther"},{"issue":"4","key":"pone.0242900.ref093","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.4049\/jimmunol.170.4.2083","article-title":"Dual roles of IL-4 in lung injury and fibrosis","volume":"170","author":"F. Huaux","year":"2003","journal-title":"J Immunol"},{"issue":"6541","key":"pone.0242900.ref094","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/376594a0","article-title":"An IL-12-based vaccination method for preventing fibrosis induced by schistosome infection","volume":"376","author":"T.A. 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