PMID: 9551917Apr 29, 1998Paper

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

The Journal of Immunology : Official Journal of the American Association of Immunologists
E W SchettinoP Casali

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 the...Continue Reading

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