Immunoglobulin variable region gene analysis to the autoantibody-secreting B cells from tumors in association with paraneoplastic autoimmune multiorgan syndrome.
OBJECTIVE
We have studied the role of lymphoproliferative tumors in the pathogenesis of autoimmune and the origin of the autoantibodies in PNP. Objectives of this study is to understand the characteristics of immunoglobulin genes of the B-cells isolated from the tumor which can produce auto-antibody.


METHODS
Total RNA of the tumor cells was then isolated and the mRNA was reversely transcribed into cDNA. V(H) and V(L) genes were amplified and cloned and their sequences were analyzed.


RESULTS
49 V(H) genes (527 to 577 bp) and 36 V(L) genes (445 to 454 bp) sequences were cloned from five tumors. All of the IgV(L) were mostly homologous to IGKV4-01 germ-line gene. The frequency of IgV(H) germ-line gene usage in a decreasing order was IGHV3-23 > IGHV3-9 > IGHV4-31 > IGHV4-59. There was more nucleotide changes occurred in complementary determining regions (CDR) than those in the framework regions (FR) in the V(H) and V(L) of B cell clones. In both V(H) and V(L), the probability (P) that the number of observed replacement mutations (R) in the CDRs would occur by random chance was low.


CONCLUSIONS
The clones of B-lymphocytes in the tumors carrying possibly functional rearranged immunoglobulin heavy and light chain genes were isolated and there were high incidences of somatic mutations in CDRs and relatively conserved sequences in framework region.
Wang
Jing
J
Department of Dermatology, Peking University First Hospital, Beijing, China.
Bu
Dingfang
D
Zhu
Xuejun
X
D000328:Adult; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D010257:Paraneoplastic Syndromes / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D016415:Sequence Alignment; D014407:Tumor Cells, Cultured
D001323:Autoantibodies; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region