Role of light chain variable region in myeloma with light chain deposition disease: evidence from an experimental model.
Light chain deposition disease (LCDD) results from a propensity of some human monoclonal L chains to form tissue deposits. We designed an experimental model for in vivo expression of human kappa L chain sequences in mice and compared a somatically mutated LCDD chain with a closely related control kappa chain, both encoded by the unique V kappa IV gene. Mice secreting the LCDD chain but not those producing the control chain showed deposits with a distribution similar to that observed in patients. These data show that discrete changes in V region sequences can play a major role in tissue deposition of human L chains.
Khamlichi
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AA
Laboratoire d'Immunologie et Génétique, CNRS URA 1172, IBMIG, Faculté des Sciences, Poitiers, France.
Rocca
A
A
Touchard
G
G
Aucouturier
P
P
Preud'homme
J L
JL
Cogné
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics; D004195:Disease Models, Animal; D005803:Genes, Immunoglobulin; D006801:Humans; D006825:Hybridomas / Q000378:metabolism / Q000637:transplantation; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D007674:Kidney Diseases / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D009194:Myeloma Proteins / Q000235:genetics*; D010265:Paraproteinemias / Q000235:genetics / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000633:toxicity; D012186:Retroperitoneal Neoplasms / Q000235:genetics / Q000473:pathology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D000911:Antibodies, Monoclonal; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D009194:Myeloma Proteins; D011993:Recombinant Fusion Proteins