Autoreactive IgG memory antibodies in patients with systemic lupus erythematosus arise from nonreactive and polyreactive precursors
- 15 July 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 105 (28) , 9727-9732
- https://doi.org/10.1073/pnas.0803644105
Abstract
Persistent autoantibody production in patients with systemic lupus erythematosus (SLE) suggests the existence of autoreactive humoral memory, but the frequency of self-reactive memory B cells in SLE has not been determined. Here, we report on the reactivity of 200 monoclonal antibodies from single IgG+ memory B cells of four SLE patients. The overall frequency of polyreactive and HEp-2 self-reactive antibodies in this compartment was similar to controls. We found 15% of IgG memory B cell antibodies highly reactive and specific for SLE-associated extractable nuclear antigens (ENA) Ro52 and La in one patient with serum autoantibody titers of the same specificity but not in the other three patients or healthy individuals. The germ-line forms of the ENA antibodies were non-self-reactive or polyreactive with low binding to Ro52, supporting the idea that somatic mutations contributed to autoantibody specificity and reactivity. Heterogeneity in the frequency of memory B cells expressing SLE-associated autoantibodies suggests that this variable may be important in the outcome of therapies that ablate this compartment.Keywords
This publication has 64 references indexed in Scilit:
- Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloningJournal of Immunological Methods, 2008
- B cell depletion therapy in systemic lupus erythematosus: long-term follow-up and predictors of responseAnnals of the Rheumatic Diseases, 2007
- CD40 ligand and MHC class II expression are essential for human peripheral B cell toleranceThe Journal of Experimental Medicine, 2007
- Mature B cells class switched to IgD are autoreactive in healthy individualsJournal of Clinical Investigation, 2007
- Autoreactivity in Human IgG+ Memory B CellsImmunity, 2007
- Igκ allelic inclusion is a consequence of receptor editingThe Journal of Experimental Medicine, 2007
- Persistent expression of autoantibodies in SLE patients in remissionThe Journal of Experimental Medicine, 2006
- Consequences of receptor editing at the λ locus: Multireactivity and light chain secretionProceedings of the National Academy of Sciences, 2006
- Light chain editing generates polyreactive antibodies in chronic graft-versus-host reactionThe Journal of Experimental Medicine, 2006
- Molecular basis of immunoglobulin variable region gene usage in systemic autoimmunityClinical and Experimental Medicine, 2005