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Restricted immunoglobulin variable region (Ig V) gene expression accompanies secondary rearrangements of light chain Ig V genes in mouse plasmacytomas
被引:14
作者:
Diaw, L
Siwarski, D
Coleman, A
Kim, J
Jones, GM
Dighiero, G
Huppi, K
机构:
[1] NCI, Genet Lab, NIH, Bethesda, MD 20892 USA
[2] Inst Pasteur, Lab Immunohematol & Immunopathol, F-75724 Paris 15, France
关键词:
V(D)J rearrangement;
plasmacytoma;
allelic exclusion;
polyreactivity;
V gene usage;
D O I:
10.1084/jem.190.10.1405
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
The many binding studies of monoclonal immunoglobulin (Ig) produced by plasmacytomas have found no universally common binding properties, but instead, groups of plasmacytomas with specific antigen-binding activities to haptens such as phosphorylcholine, dextrans, fructo-furanans, or dinitrophenyl. Subsequently, it was found that plasmacytomas with similar binding chain specificities not only expressed the same idiotype, but rearranged the same light (V-L) and heavy (V-H) variable region genes to express a characteristic monoclonal antibody. In this study, we have examined by enzyme-linked immunosorbent assay five antibodies secreted by silicone-induced mouse plasmacytomas using a broader panel of antigens including actin, myosin, tubulin, single-stranded DNA, and double-stranded DNA. We have determined the Ig heavy and light chain V gene usage in these same plasmacytomas at the DNA and RNA level. Our studies reveal: (a) antibodies secreted by plasmacytomas bind to different antigens in a manner similar to that observed for natural autoantibodies; (b) the expressed Ig heavy genes are restricted in V gene usage to the V-H-J558 family; and (c) secondary rearrangements occur at the light chain level with at least three plasmacytomas expressing both kappa and lambda light chain genes. These results suggest that plasmacytomas use a restricted population of B cells that may still be undergoing rearrangement, thereby bypassing the allelic exclusion normally associated with expression of antibody genes.
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页码:1405 / 1415
页数:11
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