Restricted Immunoglobulin Variable Region (Ig V) Gene Expression Accompanies Secondary Rearrangements of Light Chain Ig V Genes in Mouse Plasmacytomas
نویسندگان
چکیده
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 (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.
منابع مشابه
Receptor Revision of Immunoglobulin Heavy Chain Variable Region Genes in Normal Human B Lymphocytes
Contrary to the general precepts of the clonal selection theory, several recent studies have provided evidence for the secondary rearrangement of immunoglobulin (Ig) genes in peripheral lymphoid tissues. These analyses typically used transgenic mouse models and have only detected secondary recombination of Ig light chain genes. Although Ig heavy chain variable region (V(H)) genes encode a subst...
متن کاملGenomic structure of the human Ig lambda 1 gene suggests that it may be expressed as an Ig lambda 14.1-like protein or as a canonical B cell Ig lambda light chain: implications for Ig lambda gene evolution
In pre-B cells, immunoglobulin mu (Ig mu) is associated with pre-B cell-specific proteins to form a multimeric complex that is found on the cell surface. One of these proteins is encoded by the three exon Ig lambda-like gene 14.1, whose expression is restricted to pre-B cells and occurs from an unrearranged gene. A comparison of the 14.1 gene structure to the seven-gene human Ig lambda locus re...
متن کاملFunctional immunoglobulin light chain genes are replaced by ongoing rearrangements of germline V kappa genes to downstream J kappa segment in a murine B cell line
A murine B cell lymphoma (38C13) was subjected to immunoselection with mAbs directed against the idiotypic determinants of its cell surface Ig. Variants emerged with altered Ig receptors containing identical heavy chains but different light chains. The functional light chain genes in these variants were composed of V kappa segments drawn from the V kappa Ox-1 family, which had replaced the V ka...
متن کاملDetection of Pre-Malifnant B-1 Cells in NZB Mice with a Re-stricted CDR3/DFL16 Region
The relationship between the immunoglobulin (Ig) nucleotide sequence and the ability of a B cell to develop into a malignant cell was studied in a subset of B cells, B-1 cells. B-1 cells become malignant in chronic lymphocytic leukemia (CLL) and are responsible for the production of "natural autoantibodies". The autoimmune NZB mouse has been known as a human malignancy and CLL model, because ...
متن کاملHistologic transformation of follicular lymphoma to diffuse lymphoma represents tumor progression by a single malignant B cell
To investigate the clonal relationship between follicular lymphoma (FL) and transformed diffuse lymphoma (tDL), we examined the expression of tumor idiotype, immunoglobulin (Ig) gene rearrangements and sequence of Ig variable genes in paired tissue specimens. All 16 cases analyzed expressed surface immunoglobulin (sIg) on both the FL and the tDL, though the immunophenotype of one case of FL cou...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of Experimental Medicine
دوره 190 شماره
صفحات -
تاریخ انتشار 1999