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Molecular analysis of single B cells from T-cell-rich B-cell lymphoma shows the derivation of the tumor cells from mutating germinal center B cells and exemplifies means by which immunoglobulin genes are modified in germinal center B cells.
Blood. 1999 Apr 15; 93(8):2679-87.Blood

Abstract

T-cell-rich B-cell lymphoma (TCRBCL) belongs to the group of diffuse large cell lymphomas (DLL). It is characterized by a small number of tumor B cells among a major population of nonmalignant polyclonal T cells. To identify the developmental stage of the tumor progenitor cells, we micromanipulated the putative neoplastic large CD20(+) cells from TCRBCLs and amplified and sequenced immunoglobulin (Ig) V gene rearrangements from individual cells. In six cases, clonal Ig heavy, as well as light chain, gene rearrangements were amplified from the isolated B cells. All six cases harbored somatically mutated V gene rearrangements with an average mutation frequency of 15.5% for heavy (VH) and 5.9% for light (VL) chains and intraclonal diversity based on somatic mutation. These findings identify germinal center (GC) B cells as the precursors of the transformed B cells in TCRBCL. The study also exemplifies various means how Ig gene rearrangements can be modified by GC B cells or their malignant counterparts in TCRBCL: In one case, the tumor precursor may have switched from kappa to lambda light chain expression after acquiring a crippling mutation within the initially functional kappa light chain gene. In another case, the tumor cells harbor two in-frame VH gene rearrangements, one of which was rendered nonfunctional by somatic mutation. Either the tumor cell precursor entered the GC with two potentially functional in-frame rearrangements or the second VHDHJH rearrangement occurred in the GC after the initial in-frame rearrangement was inactivated by somatic mutation. Finally, in each of the six cases, at least one cell contained two (or more) copies of a clonal Ig gene rearrangement with sequence variations between these copies. The presence of sequence variants for V region genes within single B cells has so far not been observed in any other normal or transformed B lymphocyte. Fluorescence in situ hybridization (FISH) points to a generalized polyploidy of the tumor cells.

Authors+Show Affiliations

Department of Pathology, University of Frankfurt, Germany. Braeununger@em.uni-frankfurt.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10194448

Citation

Bräuninger, A, et al. "Molecular Analysis of Single B Cells From T-cell-rich B-cell Lymphoma Shows the Derivation of the Tumor Cells From Mutating Germinal Center B Cells and Exemplifies Means By Which Immunoglobulin Genes Are Modified in Germinal Center B Cells." Blood, vol. 93, no. 8, 1999, pp. 2679-87.
Bräuninger A, Küppers R, Spieker T, et al. Molecular analysis of single B cells from T-cell-rich B-cell lymphoma shows the derivation of the tumor cells from mutating germinal center B cells and exemplifies means by which immunoglobulin genes are modified in germinal center B cells. Blood. 1999;93(8):2679-87.
Bräuninger, A., Küppers, R., Spieker, T., Siebert, R., Strickler, J. G., Schlegelberger, B., Rajewsky, K., & Hansmann, M. L. (1999). Molecular analysis of single B cells from T-cell-rich B-cell lymphoma shows the derivation of the tumor cells from mutating germinal center B cells and exemplifies means by which immunoglobulin genes are modified in germinal center B cells. Blood, 93(8), 2679-87.
Bräuninger A, et al. Molecular Analysis of Single B Cells From T-cell-rich B-cell Lymphoma Shows the Derivation of the Tumor Cells From Mutating Germinal Center B Cells and Exemplifies Means By Which Immunoglobulin Genes Are Modified in Germinal Center B Cells. Blood. 1999 Apr 15;93(8):2679-87. PubMed PMID: 10194448.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular analysis of single B cells from T-cell-rich B-cell lymphoma shows the derivation of the tumor cells from mutating germinal center B cells and exemplifies means by which immunoglobulin genes are modified in germinal center B cells. AU - Bräuninger,A, AU - Küppers,R, AU - Spieker,T, AU - Siebert,R, AU - Strickler,J G, AU - Schlegelberger,B, AU - Rajewsky,K, AU - Hansmann,M L, PY - 1999/4/9/pubmed PY - 1999/4/9/medline PY - 1999/4/9/entrez SP - 2679 EP - 87 JF - Blood JO - Blood VL - 93 IS - 8 N2 - T-cell-rich B-cell lymphoma (TCRBCL) belongs to the group of diffuse large cell lymphomas (DLL). It is characterized by a small number of tumor B cells among a major population of nonmalignant polyclonal T cells. To identify the developmental stage of the tumor progenitor cells, we micromanipulated the putative neoplastic large CD20(+) cells from TCRBCLs and amplified and sequenced immunoglobulin (Ig) V gene rearrangements from individual cells. In six cases, clonal Ig heavy, as well as light chain, gene rearrangements were amplified from the isolated B cells. All six cases harbored somatically mutated V gene rearrangements with an average mutation frequency of 15.5% for heavy (VH) and 5.9% for light (VL) chains and intraclonal diversity based on somatic mutation. These findings identify germinal center (GC) B cells as the precursors of the transformed B cells in TCRBCL. The study also exemplifies various means how Ig gene rearrangements can be modified by GC B cells or their malignant counterparts in TCRBCL: In one case, the tumor precursor may have switched from kappa to lambda light chain expression after acquiring a crippling mutation within the initially functional kappa light chain gene. In another case, the tumor cells harbor two in-frame VH gene rearrangements, one of which was rendered nonfunctional by somatic mutation. Either the tumor cell precursor entered the GC with two potentially functional in-frame rearrangements or the second VHDHJH rearrangement occurred in the GC after the initial in-frame rearrangement was inactivated by somatic mutation. Finally, in each of the six cases, at least one cell contained two (or more) copies of a clonal Ig gene rearrangement with sequence variations between these copies. The presence of sequence variants for V region genes within single B cells has so far not been observed in any other normal or transformed B lymphocyte. Fluorescence in situ hybridization (FISH) points to a generalized polyploidy of the tumor cells. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/10194448/Molecular_analysis_of_single_B_cells_from_T_cell_rich_B_cell_lymphoma_shows_the_derivation_of_the_tumor_cells_from_mutating_germinal_center_B_cells_and_exemplifies_means_by_which_immunoglobulin_genes_are_modified_in_germinal_center_B_cells_ L2 - https://www.lens.org/lens/search?q=citation_id:10194448 DB - PRIME DP - Unbound Medicine ER -