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.
Details
Title
High Affinity Antibodies against Influenza Characterize the Plasmablast Response in SLE Patients After Vaccination
Author
Kaur, Kaval : University of Chicago Zheng, Nai-Ying : University of Chicago Smith, Kenneth : Oklahoma Medical Research Foundation Huang, Min : University of Chicago Li, Lie : University of Chicago Pauli, Noel T. : University of Chicago Henry Dunand, Carole J. : University of Chicago Lee, Jane-Hwei : University of Chicago Morrissey, Michael : University of Chicago Wu, Yixuan : University of Chicago Joachims, Michelle L. : Oklahoma Medical Research Foundation Munroe, Melissa E. : Oklahoma Medical Research Foundation Lau, Denise : University of Chicago Qu, Xinyan : University of Chicago Krammer, Florian : Icahn School of Medicine at Mount Sinai Wrammert, Jens : Emory University Ahmed, Rafi : Emory University James, Judith A. : Oklahoma Medical Research Foundation Wilson, Patrick C. : University of Chicago
Data availability statement
All relevant data are within the paper and its Supporting Information files.
Funding Information
National Institutes of Health, 1U19AI08724 National Institutes of Health, HHSN266200500026C National Institutes of Health, 5U54AI057158 National Institutes of Health, 5U19AI057266 National Institutes of Health, 1U19AI090023 National Institutes of Health, 1P01AI097092 National Institutes of Health, P30AR053483 National Institutes of Health, U01AI101934 National Institutes of Health, U19AI082714 National Institutes of Health, P30GM103510 National Institutes of Health, U54GM104938 National Institutes of Health, HHSN26620070010C National Institutes of Health, HHSN272201400008C University of Chicago, Gwen Knapp Center for Lupus and Immunology Research Agency of Science, Technology and Research, National Science Scholarship Austrian Science Fund, Erwin Schrödinger fellowship, J3232 Oklahoma Medical Research Foundation, Lou Kerr Chair in Biomedical Research
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.