{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kaur K"],"funding":["NIAID NIH HHS","NIAMS NIH HHS","NIGMS NIH HHS","PHS HHS"],"pagination":["e0125618"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4423960"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(5)"],"pubmed_abstract":["Breakdown of B cell tolerance is a cardinal feature of systemic lupus erythematosus (SLE). Increased numbers of autoreactive mature naïve B cells have been described in SLE patients and autoantibodies have been shown to arise from autoreactive and non-autoreactive precursors. How these defects, in the regulation of B cell tolerance and selection, influence germinal center (GC) reactions that are directed towards foreign antigens has yet to be investigated. Here, we examined the characteristics of post-GC foreign antigen-specific B cells from SLE patients and healthy controls by analyzing monoclonal antibodies generated from plasmablasts induced specifically by influenza vaccination. We report that many of the SLE patients had anti-influenza antibodies with higher binding affinity and neutralization capacity than those from controls. Although overall frequencies of autoreactivity in the influenza-specific plasmablasts were similar for SLE patients and controls, the variable gene repertoire of influenza-specific plasmablasts from SLE patients was altered, with increased usage of JH6 and long heavy chain CDR3 segments. We found that high affinity anti-influenza antibodies generally characterize the plasmablast responses of SLE patients with low levels of autoreactivity; however, certain exceptions were noted. The high-avidity antibody responses in SLE patients may also be correlated with cytokines that are abnormally expressed in lupus. These findings provide insights into the effects of dysregulated immunity on the quality of antibody responses following influenza vaccination and further our understanding of the underlying abnormalities of lupus."],"journal":["PloS one"],"pubmed_title":["High Affinity Antibodies against Influenza Characterize the Plasmablast Response in SLE Patients After Vaccination."],"pmcid":["PMC4423960"],"funding_grant_id":["HHSN272201400008C","U54 GM104938","U19 AI057266","P30GM103510","P01 AI097092","U19 AI082714","P30 GM103510","U19 AI090023","1P01AI097092","HHSN266200500026C","1U19AI090023","5U19AI057266","U54GM104938","U19AI082714","U19 AI109946","1U19AI08724","U54 AI057158","P30 AR053483","P30AR053483","5U54AI057158","T32 AI007090","U01AI101934","U01 AI101934","HHSN26620070010C"],"pubmed_authors":["James JA","Pauli NT","Wrammert J","Palese P","Huang M","Henry Dunand CJ","Munroe ME","Ahmed R","Smith K","Li L","Joachims ML","Wilson PC","Zheng NY","Krammer F","Kaur K","Lau D","Morrissey M","Qu X","Wu Y","Lee JH"],"additional_accession":[]},"is_claimable":false,"name":"High Affinity Antibodies against Influenza Characterize the Plasmablast Response in SLE Patients After Vaccination.","description":"Breakdown of B cell tolerance is a cardinal feature of systemic lupus erythematosus (SLE). Increased numbers of autoreactive mature naïve B cells have been described in SLE patients and autoantibodies have been shown to arise from autoreactive and non-autoreactive precursors. How these defects, in the regulation of B cell tolerance and selection, influence germinal center (GC) reactions that are directed towards foreign antigens has yet to be investigated. Here, we examined the characteristics of post-GC foreign antigen-specific B cells from SLE patients and healthy controls by analyzing monoclonal antibodies generated from plasmablasts induced specifically by influenza vaccination. We report that many of the SLE patients had anti-influenza antibodies with higher binding affinity and neutralization capacity than those from controls. Although overall frequencies of autoreactivity in the influenza-specific plasmablasts were similar for SLE patients and controls, the variable gene repertoire of influenza-specific plasmablasts from SLE patients was altered, with increased usage of JH6 and long heavy chain CDR3 segments. We found that high affinity anti-influenza antibodies generally characterize the plasmablast responses of SLE patients with low levels of autoreactivity; however, certain exceptions were noted. The high-avidity antibody responses in SLE patients may also be correlated with cytokines that are abnormally expressed in lupus. These findings provide insights into the effects of dysregulated immunity on the quality of antibody responses following influenza vaccination and further our understanding of the underlying abnormalities of lupus.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015","modification":"2024-10-19T03:19:23.671Z","creation":"2019-03-26T23:32:38Z"},"accession":"S-EPMC4423960","cross_references":{"pubmed":["25951191"],"doi":["10.1371/journal.pone.0125618"]}}