High Affinity Antibodies against Influenza Characterize the Plasmablast Response in SLE Patients After Vaccination
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Date
2015-05-07Author
Kaval Kaur
Nai-Ying Zheng
Kenneth Smith
Min Huang
Lie Li
Noel T. Pauli
Carole J. Henry Dunand
Jane-Hwei Lee
Michael Morrissey
Yixuan Wu
Michelle L. Joachims
Melissa E. Munroe
Denise Lau
Xinyan Qu
Florian Krammer
Jens Wrammert
Peter Palese
Rafi Ahmed
Judith A. James
Patrick C. Wilson
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Show full item recordAbstract
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.
Citation
Kaur K, Zheng N-Y, Smith K, Huang M, Li L, Pauli NT, et al. (2015) High Affinity Antibodies against Influenza Characterize the Plasmablast Response in SLE Patients After Vaccination. PLoS ONE 10(5): e0125618. doi:10.1371/journal.pone.0125618