title: High Affinity Antibodies against Influenza Characterize the Plasmablast Response in SLE Patients After Vaccination.
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.
authors.affiliation: Committee on Immunology, The University of Chicago, Chicago, Illinois, United States of America; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Kaval
authors.initials: K
authors.lastname: Kaur
authors.affiliation: Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Nai-Ying
authors.initials: NY
authors.lastname: Zheng
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Smith
authors.affiliation: Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Lie
authors.initials: L
authors.lastname: Li
authors.affiliation: Committee on Immunology, The University of Chicago, Chicago, Illinois, United States of America; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Noel T
authors.initials: NT
authors.lastname: Pauli
authors.affiliation: Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Carole J
authors.initials: CJ
authors.lastname: Henry Dunand
authors.affiliation: Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Jane-Hwei
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Morrissey
authors.affiliation: Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Joachims
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Munroe
authors.affiliation: Committee on Immunology, The University of Chicago, Chicago, Illinois, United States of America; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Denise
authors.initials: D
authors.lastname: Lau
authors.affiliation: Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Florian
authors.initials: F
authors.lastname: Krammer
authors.affiliation: Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Jens
authors.initials: J
authors.lastname: Wrammert
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
authors.affiliation: Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America; Department of Medicine and Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
authors.affiliation: Committee on Immunology, The University of Chicago, Chicago, Illinois, United States of America; Department of Medicine, Section of Rheumatology, The Knapp Center for Lupus and Immunology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Wilson
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D000917:Antibody Formation; D016022:Case-Control Studies; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D009975:Orthomyxoviridae / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007252:Influenza Vaccines