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Analysis of immunoglobulin variable region genes from human IgG anti‐DNA hybridomas

1992; Wiley; Volume: 22; Issue: 7 Linguagem: Inglês

10.1002/eji.1830220709

1521-4141

Thomas Winkler, Holger Fehr, Joachim R. Kalden,

Chronic Lymphocytic Leukemia Research

Abstract The molecular mechanisms leading to anti‐double‐stranded (ds)DNA antibody production in systemic lupus erythematosus (SLE) are poorly understood. We describe here the immunoglobulin variable region genes of six human hybridomas secreting IgG anti‐dsDNA antibodies derived from three SLE patients. The monoclonal IgG anti‐dsDNA antibodies have been shown to be of high affinity and no multireactivity was observed (Winkler et al., Clin. Exp. Immunol. , 1991. 85: 379). The comparison of the variable region genes expressed in the hybridomas with known germ‐line genes as well as with the germ‐line counterparts from one patient shows that the V H and V L sequences are somatically mutated. The pattern and extent of the observed somatic mutations are suggestive for an antigen‐driven selection of at least four of these B cell clones. Several V H and V L genes used by the hybridomas were found to be expressed in the natural antibody repertoire, in the restricted fetal repertoire and in B cell malignancies expressing the CD5 antigen.