High-Frequency Expression of a Conserved κ Light-Chain Variable-Region Gene in Chronic Lymphocytic Leukemia

• Published in: Proceedings of the National Academy of Sciences - PNAS 1987-05, Vol.84 (9), p.2916-2920
• Main Authors: Kipps, Thomas J., Fong, Sherman, Tomhave, Eric, Chen, Pojen P., Goldfien, Robert D., Carson, Dennis A.
• Format: Article
• Language: English
• Subjects: Antibodies; B lymphocytes; B-Lymphocytes - immunology; Base Sequence; Biological and medical sciences; Cell lines; Chronic lymphocytic leukemia; Fundamental and applied biological sciences. Psychology; Gene expression; Genes; Humans; Hybridomas; Immunoglobulin G - genetics; Immunoglobulin kappa-Chains - genetics; Immunoglobulin Light Chains - genetics; Immunoglobulin M - genetics; Immunoglobulin Variable Region - genetics; Leukemia, Lymphoid - genetics; Leukemia, Lymphoid - immunology; Lymphocytes; Molecular and cellular biology; Molecular genetics; Monoclonal antibodies; Nucleic Acid Hybridization; Oligonucleotide probes; Oligonucleotides; RNA
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.9.2916

Malignant B lymphocytes from several patients with chronic lymphocytic leukemia (CLL) were examined for reactivity with murine monoclonal antibody 17.109. This antibody, prepared against the rheumatoid factor (RF) paraprotein Sie, recognizes a crossreactive idiotype on 48% of human IgM RF paraproteins, but does not react with IgM paraproteins without RF activity or substantially with normal pooled immunoglobulin. The 17.109-reactive idiotype is a marker for a κ III variable-region gene, designated VκRF, that is conserved in outbred human populations. In a limited study of 31 CLL patients, the leukemic cells from 5 of 20 patients with κ light chain-expressing CLL were recognized by the 17.109 monoclonal antibody. Despite having malignant cells specifically reactive with this antibody, patients with 17.109-positive CLL did not have elevated serum levels of circulating antibody bearing 17.109-reactive determinants. Total RNAs isolated from the CLL B lymphocytes, or from hybridomas produced by fusing the CLL cells with the WI-L2-729-HF2cell line, were fractionated electrophoretically and examined by blot hybridization. Under stringent hybridization conditions capable of discerning a single base-pair mismatch, RNA from the 17.109-idiotype-positive CLL cells hybridized to synthetic oligonucleotide probes corresponding to framework and complementary-determining regions in the VκRF gene. The high frequency of the 17.109-associated idiotype and the VκRF gene in CLL suggests that the disease may arise from B lymphocytes that express a restricted set of inherited immunoglobulin variable-region genes with little or no somatic mutation.