Lupus-specific antibodies reveal an altered pattern of somatic mutation

Audrey J. Manheimer-Lory, Gisele Zandman-Goddard, Anne Davidson, Cynthia Aranow, Betty Diamond*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


The F4 idiotype is a heavy chain determinant expressed almost exclusively on IgG immunoglobulins and is highly associated with specificity for double-stranded DNA. Since high-titered F4 expression is present predominantly in sera of patients with systemic lupus erythematosus (SLE), we thought F4+ IgG antibodies might constitute a useful subset of immunoglobulins in which to investigate lupus-specific alterations in variable (V) region gene expression or in the process of somatic mutation. This molecular analysis of F4+ B cell lines generated from lupus patients demonstrates that despite the strong association of F4 reactivity with specificity for native DNA, there is no apparent V(H) gene restriction. Furthermore, V(H) gene segments encoding these antibodies are also used in protective immune responses. An examination of the process of somatic mutation in F4+ antibodies showed no abnormality in frequency of somatic mutation nor in the distribution of mutations in complementarity-determining regions or framework regions. However, there was a decrease in targeting of mutations to putative mutational hot spots. This subtle difference in mutations present in these antibodies may reflect an intrinsic defect in mutational machinery or, more likely, altered state of B cell activation that affects the mutational process and perhaps also negative selection.

Original languageEnglish
Pages (from-to)2538-2546
Number of pages9
JournalJournal of Clinical Investigation
Issue number10
StatePublished - 15 Nov 1997
Externally publishedYes


FundersFunder number
National Institute of Arthritis and Musculoskeletal and Skin DiseasesR01AR032371
National Institute of Arthritis and Musculoskeletal and Skin Diseases


    • Anti-double-stranded DNA antibody
    • Autoreactivity
    • Idiotyp
    • Mutational hot spot
    • Variable region gene expression


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