High Affinity Antibodies against Influenza Characterize the Plasmablast Response in SLE Patients After Vaccination

作者：Kaval Kaur, Nai‐Ying Zheng, Kenneth G. C. Smith, Min Huang, Lie Li, Noel T. Pauli, Carole J. Henry Dunand, Jane-Hwei Lee, Morrissey Michael, 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 · 发表于：PLoS ONE · 年份：2015 · DOI：10.1371/journal.pone.0125618 · 被引用次数：35 · 研究领域：Systemic Lupus Erythematosus Research、T-cell and B-cell Immunology、Immune Cell Function and Interaction

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 e...