Centers and Institutes
Published May 7, 2015 | Version v1
Journal article Open

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

Creators

  • 1. University of Chicago
  • 2. Oklahoma Medical Research Foundation
  • 3. Icahn School of Medicine at Mount Sinai
  • 4. Emory University

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.

Data availability

All relevant data are within the paper and its Supporting Information files.

Files

journal.pone.0125618.pdf

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Additional details

Identifiers

DOI
10.1371/journal.pone.0125618
Other
oai:uchicago.tind.io:9587

Funding

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
Oklahoma Medical Research Foundation
Lou Kerr Chair in Biomedical Research

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Immunology, Medicine
Center(s) or Institute(s)
Gwen Knapp Center for Lupus and Immunology Research