The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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© The Rockefeller University Press, 0022-1007/1999/11/1405/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 10, November 15, 1999 1405-1416

Original Article

Restricted Immunoglobulin Variable Region (Ig V) Gene Expression Accompanies Secondary Rearrangements of Light Chain Ig V Genes in Mouse Plasmacytomas

Lena Diawa, David Siwarskia, Allen Colemana, Jennifer Kima, Gary M. Jonesa, Guillaume Dighierob, and Konrad Huppia

a Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892
b Laboratoire d'Immunohematologie et Immunopathologie, Institut Pasteur, 75724 Paris Cedex 15, France
Laboratory of Genetics, National Cancer Institute, NIH, Bldg. 37, Rm. 2B-21, Bethesda, MD 20892.301-402-1031301-496-5992

huppi{at}helix.nih.gov

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, fructofuranans, or dinitrophenyl. Subsequently, it was found that plasmacytomas with similar binding chain specificities not only expressed the same idiotype, but rearranged the same light (VL) and heavy (VH) 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 VH-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.

Key Words: V(D)J rearrangement • plasmacytoma • allelic exclusion • polyreactivity • V gene usage

1used in this paper: CLL, chronic lymphocytic leukemia; ds, double-stranded; g, generation; GC, germinal center; IVS, intervening sequence; NAA, natural polyreactive autoantibody; PC, plasmacytoma; R, replacement; RAG, recombination activating gene; RT, reverse transcription; S, silent; SI, silicone-induced PC; ss, single-stranded

© 1999 The Rockefeller University Press


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