These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Myeloma VL and VH gene sequences reveal a complementary imprint of antigen selection in tumor cells.
    Author: Sahota SS, Leo R, Hamblin TJ, Stevenson FK.
    Journal: Blood; 1997 Jan 01; 89(1):219-26. PubMed ID: 8978295.
    Abstract:
    In multiple myeloma, sequence studies of VH genes used to encode clonal Ig in neoplastic plasma cells have shown a common pattern of extensive somatic hypermutation. A further consistent feature of these VH sequences is a complete lack of intraclonal variation. These findings indicate that the malignant cell arises at a mature, postfollicular stage of B-cell development. However, only a minority of cases have a distribution of somatic mutations in VH consistent with a prior role for antigen in selecting the B cell of origin. To complement these studies, and to take further the investigation of a role for antigen in the clonal history of myeloma, we have investigated tumor-derived VL sequences from bone marrows of 15 patients. All sequences (9V kappa and 6V lambda A) were potentially functional and 5 of 15 had evidence for N-region additions. All had undergone extensive somatic hypermutation, and showed no intraclonal variation. In 4 of 15 cases, the distribution of mutations revealed a significant (P < .05) clustering of replacement mutations in the CDR sequences, indicating a role for VL in selection by antigen. Comparison with the VH sequences used by the same tumor cells showed that, if significant clustering was present, it was in either VH or VL but not both. Altogether, 10 of 15 V-regions showed evidence for antigen selection, suggesting that the B cell of origin has behaved as a normal germinal center B cell. Deductions concerning a role for antigen selection may require both VH and VL sequences for validation.
    [Abstract] [Full Text] [Related] [New Search]