Intraclonal diversification of immunoglobulin light chains in a subset of chronic lymphocytic leukemia alludes to antigen-driven clonal evolution.

Abstract:

:The study of intraclonal diversification (ID) in immunoglobulin (IG) genes offers valuable insight into the role of ongoing interactions with antigen in lymphomagenesis. We recently showed that ID in the IG heavy chain genes of patients with chronic lymphocytic leukemia (CLL) was generally limited; however, intense ID was evident in selected cases, especially those expressing stereotyped IGHV4-34 rearrangements and assigned to subset 4. Here, we report results from a large-scale subcloning study of IG light variable genes, in a total of 1008 subcloned sequences from 56 CLL cases. Multiple analogies were noted between heavy and light chains regarding the occurrence and molecular features of ID. More specifically, the impact of ID on the clonotypic light chains was generally low, with the significant exception of subset 4. Similar to the IGHV4-34 heavy chains of this subset, their partner IGKV2-30 light chains were affected by an active and precisely targeted ID process. Altogether, these findings strengthen the argument that stereotypy in subset 4 extends to stereotyped ID patterns for both heavy and light chains through persistent antigenic stimulation. Furthermore, they strongly suggest that light chains have an active role in the antigen selection process, at least for certain subsets of CLL cases.

journal_name

Leukemia

journal_title

Leukemia

authors

Kostareli E,Sutton LA,Hadzidimitriou A,Darzentas N,Kouvatsi A,Tsaftaris A,Anagnostopoulos A,Rosenquist R,Stamatopoulos K

doi

10.1038/leu.2010.90

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

1317-24

issue

7

eissn

0887-6924

issn

1476-5551

pii

leu201090

journal_volume

24

pub_type

杂志文章,多中心研究

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