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Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia.
- Source :
-
Blood [Blood] 2004 Nov 01; Vol. 104 (9), pp. 2879-85. Date of Electronic Publication: 2004 Jun 24. - Publication Year :
- 2004
-
Abstract
- We recently identified a chronic lymphocytic leukemia (CLL) subgroup using the immunoglobulin variable heavy-chain (V(H)) gene V(H)3-21 with almost identical heavy-chain complementarity determining region 3s (HCDR3s) and preferential variable light-chain (V(L)) gene usage, suggesting recognition of a common antigen epitope in this subset. To further explore the B-cell receptors (BCRs) in CLL, we characterized 407 V(H) rearrangements amplified from 346 CLLs regarding V(H), diversity (D), and joining (J(H)) gene usage and performed multiple alignment of the HCDR3 sequences. These analyses revealed 3 small subsets (2 V(H)1-69 groups, 7 cases; and 1 V(H)1-2 group, 5 cases) with highly restricted HCDR3 features including identical V(H)/D/J(H) usage, HCDR3 lengths, and shared N-sequences, in addition to the V(H)3-21 group (22 cases). Furthermore, another 3 groups (9 V(H)1-3(+) cases, 3 V(H)1-18(+) cases, and 5 V(H)4-39(+) cases) had essentially identical V(H)/D/J(H) use and similar HCDR3 lengths but less conserved N-regions. Analysis in all 6 of these subgroups showed restriction in V(L) gene use, whereas no association between V(H) and V(L) usage was found in cases without HCDR3 similarities. Altogether, structurally similar HCDR3s associated with preferential V(L) gene usage implies selection of BCRs, especially in subsets showing high HCDR3 similarities, thus pointing to restricted antigen recognition sites and possibly involvement of specific antigens in CLL development.
- Subjects :
- Adult
Aged
Aged, 80 and over
Amino Acid Sequence
B-Lymphocyte Subsets classification
B-Lymphocyte Subsets immunology
Complementarity Determining Regions genetics
Female
Gene Rearrangement, B-Lymphocyte, Heavy Chain genetics
Gene Rearrangement, B-Lymphocyte, Heavy Chain immunology
Gene Rearrangement, B-Lymphocyte, Light Chain genetics
Gene Rearrangement, B-Lymphocyte, Light Chain immunology
Humans
Leukemia, Lymphocytic, Chronic, B-Cell etiology
Male
Middle Aged
Receptors, Antigen, B-Cell genetics
Receptors, Antigen, B-Cell immunology
Sequence Alignment
B-Lymphocyte Subsets pathology
Epitopes, B-Lymphocyte immunology
Gene Rearrangement, B-Lymphocyte immunology
Leukemia, Lymphocytic, Chronic, B-Cell immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 104
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 15217826
- Full Text :
- https://doi.org/10.1182/blood-2004-01-0132