Defining origins of malignant B cells: a new circulating normal human IgM+D+ B-cell subset lacking CD27 expression and displaying somatically mutated IGHV genes as a relevant memory population
Defining origins of malignant B cells: a new circulating normal human IgM+D+ B-cell subset lacking CD27 expression and displaying somatically mutated IGHV genes as a relevant memory population
In probing the cell of origin in malignant B cells, an imprint of somatic hypermutation (SHM) in immunoglobulin (Ig) variable (V) region genes delineates antigen encounter, and identifying the precise pathway generating SHM in the normal B-cell counterpart becomes relevant. SHM remains the definitive memory imprint in normal human B cells, but CD27 expression also delineates memory. Recently, dye extrusion adenosine triphosphate-binding transporter assays identified circulating isotype-switched memory B cells that lacked CD27, yet exhibited low levels of SHM. To extend findings, we report a pre-switched CD27-ve circulating memory B-cell population in normal blood using comparable assays, and isolated CD19+IgM+D+CD27-ve cells (>99% purity) for the analysis of IGHV5/IGHV3-IGHM transcripts. Of these (n=334), 78% were germ line and naive B cell derived. Strikingly, 21.9% of the transcripts were mutated. They showed 3–5 mutations (13.5% of sequences) and >5 mutations (8.4% of sequences) per transcript. Accrual of mutations in a subset of CD19+IgM+D+CD27-ve cells define a new circulating pre-switched memory B-cell pool, present in substantial numbers in the population harboring naive B cells. These CD19+IgM+D+CD27-ve memory B cells may have a distinct lineage and function, and seem relevant to understanding origins of malignant B cells, in particular those of hairy cell leukemia cells, which display mutated V genes yet lack CD27 expression.
cd27, normal b-cell memory, somatic hypermutation, hairy cell leukemia
2075-2080
Weston-Bell, N.
c99c8c28-519f-4c3e-bd8c-679995a0472e
Townsend, M.
08e4f0af-4360-402b-a3a3-a96a31f7918d
Di Genova, G.
3f78f1ac-d2d2-439b-bd24-c66f04634778
Forconi, F.
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Sahota, S.S.
66c1457f-cba2-4c49-9c8c-fcee0748b6b8
November 2009
Weston-Bell, N.
c99c8c28-519f-4c3e-bd8c-679995a0472e
Townsend, M.
08e4f0af-4360-402b-a3a3-a96a31f7918d
Di Genova, G.
3f78f1ac-d2d2-439b-bd24-c66f04634778
Forconi, F.
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Sahota, S.S.
66c1457f-cba2-4c49-9c8c-fcee0748b6b8
Weston-Bell, N., Townsend, M., Di Genova, G., Forconi, F. and Sahota, S.S.
(2009)
Defining origins of malignant B cells: a new circulating normal human IgM+D+ B-cell subset lacking CD27 expression and displaying somatically mutated IGHV genes as a relevant memory population.
Leukemia, 23 (11), .
(doi:10.1038/leu.2009.178).
(PMID:19776762)
Abstract
In probing the cell of origin in malignant B cells, an imprint of somatic hypermutation (SHM) in immunoglobulin (Ig) variable (V) region genes delineates antigen encounter, and identifying the precise pathway generating SHM in the normal B-cell counterpart becomes relevant. SHM remains the definitive memory imprint in normal human B cells, but CD27 expression also delineates memory. Recently, dye extrusion adenosine triphosphate-binding transporter assays identified circulating isotype-switched memory B cells that lacked CD27, yet exhibited low levels of SHM. To extend findings, we report a pre-switched CD27-ve circulating memory B-cell population in normal blood using comparable assays, and isolated CD19+IgM+D+CD27-ve cells (>99% purity) for the analysis of IGHV5/IGHV3-IGHM transcripts. Of these (n=334), 78% were germ line and naive B cell derived. Strikingly, 21.9% of the transcripts were mutated. They showed 3–5 mutations (13.5% of sequences) and >5 mutations (8.4% of sequences) per transcript. Accrual of mutations in a subset of CD19+IgM+D+CD27-ve cells define a new circulating pre-switched memory B-cell pool, present in substantial numbers in the population harboring naive B cells. These CD19+IgM+D+CD27-ve memory B cells may have a distinct lineage and function, and seem relevant to understanding origins of malignant B cells, in particular those of hairy cell leukemia cells, which display mutated V genes yet lack CD27 expression.
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Published date: November 2009
Keywords:
cd27, normal b-cell memory, somatic hypermutation, hairy cell leukemia
Organisations:
Cancer Sciences
Identifiers
Local EPrints ID: 73013
URI: http://eprints.soton.ac.uk/id/eprint/73013
ISSN: 0887-6924
PURE UUID: c802a477-895c-4df3-9e13-11e6fb71b88f
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Date deposited: 01 Mar 2010
Last modified: 14 Mar 2024 02:57
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Contributors
Author:
N. Weston-Bell
Author:
M. Townsend
Author:
G. Di Genova
Author:
S.S. Sahota
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