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PMID: 9551917 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Lack of intraclonal diversification in Ig heavy and light chain V region genes expressed by CD5+IgM+ chronic lymphocytic leukemia B cells: a multiple time point analysis.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 160 ·No. 2 ·1998-01-15 ·Pages 820-30

Schettino EW, Cerutti A, Chiorazzi N, Casali P

Abstract

To analyze the modalities of clonal expansion of chronic lymphocytic leukemia (CLL) cells, we sequenced at multiple time points the V(D)J genes expressed by CD5+IgM+CLL B cells in three patients. All three V(D)J gene sequences were found to be point mutated. The mutation frequency in the Ig VH (3.96 x 10(-2) and 2.41 x 10(-2) change/bp) and Vkappa and Vlambda (6.67 x 10(-2) and 1.74 x 10(-2) change/bp) genes of two CLLs (1.19 and 1.32, respectively) was similar, and higher than that in the corresponding gene segments of the third CLL (1.69; 3.4 x 10(-3) and 6.67 x 10(-3) change/bp). In all three CLLs, there was no preferential representation of nucleotide changes yielding amino acid replacement (R mutations), nor was there any preferential segregation of R mutations within the Ig V gene complementarity-determining regions. In all three CLLs, the somatic mutations were all identical in multiple Ig VHDJH transcripts at any given time point, and were all conserved at multiple time points throughout a 2-yr period. The lack of concentration of R mutations in the complementarity-determining regions and the lack of intraclonal heterogeneity suggest that Ag may no longer be able to play a significant role in the clonal expansion of these cells. This conclusion would be strengthened further by the germline configuration of the bcl-1 and bcl-2 proto-oncogenes that are translocated in neoplastic B cells that display significant traces of intraclonal diversification and Ag-dependent selection, such as B-prolymphocytic leukemia and low grade follicular non-Hodgkin lymphoma.

MeSH Terms
Aged Amino Acid Sequence B-Lymphocytes/metabolism Base Sequence CD5 Antigens/genetics Clone Cells DNA Mutational Analysis Gene Expression Regulation, Neoplastic/immunology Gene Rearrangement, B-Lymphocyte Genes, Immunoglobulin Genes, bcl-1/immunology Genes, bcl-2/immunology Humans Immunoglobulin Heavy Chains/biosynthesis,genetics Immunoglobulin Light Chains/biosynthesis,genetics Immunoglobulin M/genetics Immunoglobulin Variable Region/biosynthesis,genetics Immunoglobulin kappa-Chains/genetics Immunoglobulin lambda-Chains/genetics Immunophenotyping Leukemia, Lymphocytic, Chronic, B-Cell/genetics,immunology Male Molecular Sequence Data Point Mutation
Chemicals
CD5 Antigens Immunoglobulin Heavy Chains Immunoglobulin Light Chains Immunoglobulin M Immunoglobulin Variable Region Immunoglobulin kappa-Chains Immunoglobulin lambda-Chains
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Schettino E W
Department of Pathology, Cornell University Medical College, New York 10021, USA.
Cerutti A
Chiorazzi N
Casali P
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Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
0022-1767
Published
1998-01-15
Pages
820-30
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC4625536
Subset
IM
Grants
NIAMS NIH HHS · R01 AR040908 · United States
NIAID NIH HHS · AI 10811 · United States
NIAMS NIH HHS · AR 40908 · United States
NCI NIH HHS · CA 68541 · United States
Databases
GENBANK
U31936, U31937, U31962, U31963, U31964, U31965
External Links
PubMed source PMC Full Text View journal details
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