The normal IGHV1-69-derived B-cell repertoire contains stereotypic patterns characteristic of unmutated CLL
The normal IGHV1-69-derived B-cell repertoire contains stereotypic patterns characteristic of unmutated CLL
The cell of origin of chronic lymphocytic leukemia (CLL) has long been sought, and immunoglobulin gene analysis provides new clues. In the unmutated subset (U-CLL), there is increased usage of the 51p1-related alleles of the immunoglobulin heavy chain variable 1-69 gene, often combined with selected genes and with immunoglobulin heavy chain diversity IGHJ6. Stereotypic characteristics of the HCDR3 result and suggest antigen selection of the leukemic clones. We have now analyzed 51p1/IGHJ6 combinations in normal blood B cells from 3 healthy persons for parallel sequence patterns. A high proportion (33.3% of sequences) revealed stereotypic patterns, with several (15.0%) being similar to those described in U-CLL. Previously unreported CLL-associated stereotypes were detected in 4.8%. Stereotypes (13.6%) not detected in CLL also were found. The HCDR2-IGHJ6 sequences were essentially unmutated. Junctional amino acids in normal B cells were heterogeneous, as in cases of stereotyped CLL. Phenotypically, normal B cells expressing 51p1-derived immunoglobulin M were naive. This snapshot of the naive B-cell repertoire reveals subsets of B cells closely related to those characteristic of CLL. Conserved patterns in the 51p1-encoded immunoglobulin M of normal B cells suggest a restricted sequence repertoire shaped by evolution to recognize common pathogens. Proliferative pressure on these cells is the likely route to U-CLL.
71-77
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Potter, Kathleen N.
86a99047-494b-405b-a3f7-650c1dcd5838
Wheatley, Isla
a6564fc5-68c6-476d-a3e4-e86c1be33fc4
Darzentas, Nikos
a94339af-f185-4ea8-8127-3eba5f675298
Sozzi, Elisa
e811ff23-6fe9-47ec-b052-fe8d34d1e36b
Stamatopoulos, Kostas
04185c9f-28ac-4693-bcff-4b6f2081de5c
Mockridge, C. Ian
327aef17-4837-4f2a-a93b-3d17cd1a7f9f
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
7 January 2010
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Potter, Kathleen N.
86a99047-494b-405b-a3f7-650c1dcd5838
Wheatley, Isla
a6564fc5-68c6-476d-a3e4-e86c1be33fc4
Darzentas, Nikos
a94339af-f185-4ea8-8127-3eba5f675298
Sozzi, Elisa
e811ff23-6fe9-47ec-b052-fe8d34d1e36b
Stamatopoulos, Kostas
04185c9f-28ac-4693-bcff-4b6f2081de5c
Mockridge, C. Ian
327aef17-4837-4f2a-a93b-3d17cd1a7f9f
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Forconi, Francesco, Potter, Kathleen N., Wheatley, Isla, Darzentas, Nikos, Sozzi, Elisa, Stamatopoulos, Kostas, Mockridge, C. Ian, Packham, Graham and Stevenson, Freda K.
(2010)
The normal IGHV1-69-derived B-cell repertoire contains stereotypic patterns characteristic of unmutated CLL.
Blood, 115 (1), .
(doi:10.1182/blood-2009-06-225813).
(PMID:19887677)
Abstract
The cell of origin of chronic lymphocytic leukemia (CLL) has long been sought, and immunoglobulin gene analysis provides new clues. In the unmutated subset (U-CLL), there is increased usage of the 51p1-related alleles of the immunoglobulin heavy chain variable 1-69 gene, often combined with selected genes and with immunoglobulin heavy chain diversity IGHJ6. Stereotypic characteristics of the HCDR3 result and suggest antigen selection of the leukemic clones. We have now analyzed 51p1/IGHJ6 combinations in normal blood B cells from 3 healthy persons for parallel sequence patterns. A high proportion (33.3% of sequences) revealed stereotypic patterns, with several (15.0%) being similar to those described in U-CLL. Previously unreported CLL-associated stereotypes were detected in 4.8%. Stereotypes (13.6%) not detected in CLL also were found. The HCDR2-IGHJ6 sequences were essentially unmutated. Junctional amino acids in normal B cells were heterogeneous, as in cases of stereotyped CLL. Phenotypically, normal B cells expressing 51p1-derived immunoglobulin M were naive. This snapshot of the naive B-cell repertoire reveals subsets of B cells closely related to those characteristic of CLL. Conserved patterns in the 51p1-encoded immunoglobulin M of normal B cells suggest a restricted sequence repertoire shaped by evolution to recognize common pathogens. Proliferative pressure on these cells is the likely route to U-CLL.
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Published date: 7 January 2010
Organisations:
Cancer Sciences
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Local EPrints ID: 149437
URI: http://eprints.soton.ac.uk/id/eprint/149437
ISSN: 0006-4971
PURE UUID: c4e212a6-b9a2-4070-96d1-1b81ea395d1b
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Date deposited: 30 Apr 2010 14:19
Last modified: 14 Mar 2024 02:57
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Author:
Isla Wheatley
Author:
Nikos Darzentas
Author:
Elisa Sozzi
Author:
Kostas Stamatopoulos
Author:
C. Ian Mockridge
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