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
Leukemiajournal_title
Leukemiaauthors
Kostareli E,Sutton LA,Hadzidimitriou A,Darzentas N,Kouvatsi A,Tsaftaris A,Anagnostopoulos A,Rosenquist R,Stamatopoulos Kdoi
10.1038/leu.2010.90subject
Has Abstractpub_date
2010-07-01 00:00:00pages
1317-24issue
7eissn
0887-6924issn
1476-5551pii
leu201090journal_volume
24pub_type
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