Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Mol Med. 2008 Nov-Dec;14(11-12):675-81. doi: 10.2119/2008-00066.Zhang. Epub 2008 Jul 30.

Pathogenic autoantibodies in systemic lupus erythematosus are derived from both self-reactive and non-self-reactive B cells.

Author information

1
The Center for Autoimmune and Musculoskeletal Disease, Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, New York 11030, USA.

Abstract

Previous studies have shown that both murine and human anti-double-stranded DNA (anti-dsDNA) antibodies can develop from non-DNA-reactive B cells and suggest a crucial role for somatic mutation in dsDNA binding. However, since only a limited number of human anti-dsDNA antibodies have been analyzed previously, we could not exclude other mechanisms for the generation of anti-dsDNA antibodies in patients with systemic lupus erythematosus (SLE). Therefore, we isolated IgM anti-dsDNA antibodies from peripheral blood B cells of a patient with SLE. Three somatically mutated IgM anti-DNA antibodies with pathogenic potential (glomerular binding) were reverted to their germline configuration. Although all three IgM anti-dsDNA antibodies came from the same lupus patient, they displayed different profiles. Reversion to the germline sequence of autoantibodies A9 and B5 resulted in decreased dsDNA binding. In contrast, the germline form of G3-recognized dsDNA as well as the mutated counterpart. These results suggest that mutated IgM anti-dsDNA antibodies may develop from both DNA- and non-DNA-reactive B cells. The implications are that B cell activation occurs in response to self and non-self antigens, while selection after activation may be mediated by self antigen in SLE. Moreover, ineffective tolerance checkpoints may exist before and after antigen activation in SLE.

PMID:
18677426
PMCID:
PMC2493535
DOI:
10.2119/2008-00066.Zhang
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Feinstein Institute Icon for PubMed Central
Loading ...
Support Center