High Affinity Antibodies against Influenza Characterize the Plasmablast Response in SLE Patients After Vaccination
| Autor: | Noel T. Pauli, Peter Palese, Carole J. Henry Dunand, Kaval Kaur, Kenneth J. Smith, Min Huang, Michelle L. Joachims, Xinyan Qu, Florian Krammer, Rafi Ahmed, Patrick C. Wilson, Yixuan Wu, Jens Wrammert, Jane-Hwei Lee, Melissa E. Munroe, Li L, Denise Lau, Nai-Ying Zheng, Michael Morrissey, Judith A. James |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Naive B cell
Antibody Affinity lcsh:Medicine 03 medical and health sciences 0302 clinical medicine Antigen immune system diseases medicine Humans Lupus Erythematosus Systemic skin and connective tissue diseases lcsh:Science B cell 030304 developmental biology 030203 arthritis & rheumatology 0303 health sciences Multidisciplinary Lupus erythematosus Systemic lupus erythematosus biology lcsh:R Autoantibody Antibodies Monoclonal Germinal center Orthomyxoviridae medicine.disease Virology 3. Good health medicine.anatomical_structure Influenza Vaccines Case-Control Studies Antibody Formation Immunology biology.protein lcsh:Q Antibody |
| Zdroj: | PLoS ONE, Vol 10, Iss 5, p e0125618 (2015) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|