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Chronic lymphocytic leukemia: revelations from the B-cell receptor

Chronic lymphocytic leukemia: revelations from the B-cell receptor
Chronic lymphocytic leukemia: revelations from the B-cell receptor
The finding that chronic lymphocytic leukemia (CLL) consists of 2 clinical subsets, distinguished by the incidence of somatic mutations in the immunoglobulin (Ig) variable region (V) genes, has clearly linked prognosis to biology. Antigen encounter by the cell of origin is indicated in both subsets by selective but distinct expression of V genes, with evidence for continuing stimulation after transformation. The key to distinctive tumor behavior likely relates to the differential ability of the B-cell receptor (BCR) to respond. Both subsets may be undergoing low-level signaling in vivo, although analysis of blood cells limits knowledge of critical events in the tissue microenvironment. Analysis of signal competence in vitro reveals that unmutated CLL generally continues to respond, whereas mutated CLL is anergized. Differential responsiveness may reflect the increased ability of post-germinal center B cells to be triggered by antigen, leading to long-term anergy. This could minimize cell division in mutated CLL and account for prognostic differences. Unifying features of CLL include low responsiveness, expression of CD25, and production of immunosuppressive cytokines. These properties are reminiscent of regulatory T cells and suggest that the cell of origin of CLL might be a regulatory B cell. Continuing regulatory activity, mediated via autoantigen, could suppress Ig production and lead to disease-associated hypogammaglobulinemia.
0006-4971
4389-4395
Stevenson, F.K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Caligaris-Cappio, F.
ba55c405-f1bd-4fa8-96c2-a2925e1bd508
Stevenson, F.K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Caligaris-Cappio, F.
ba55c405-f1bd-4fa8-96c2-a2925e1bd508

Stevenson, F.K. and Caligaris-Cappio, F. (2004) Chronic lymphocytic leukemia: revelations from the B-cell receptor. Blood, 103 (12), 4389-4395. (doi:10.1182/blood-2003-12-4312).

Record type: Article

Abstract

The finding that chronic lymphocytic leukemia (CLL) consists of 2 clinical subsets, distinguished by the incidence of somatic mutations in the immunoglobulin (Ig) variable region (V) genes, has clearly linked prognosis to biology. Antigen encounter by the cell of origin is indicated in both subsets by selective but distinct expression of V genes, with evidence for continuing stimulation after transformation. The key to distinctive tumor behavior likely relates to the differential ability of the B-cell receptor (BCR) to respond. Both subsets may be undergoing low-level signaling in vivo, although analysis of blood cells limits knowledge of critical events in the tissue microenvironment. Analysis of signal competence in vitro reveals that unmutated CLL generally continues to respond, whereas mutated CLL is anergized. Differential responsiveness may reflect the increased ability of post-germinal center B cells to be triggered by antigen, leading to long-term anergy. This could minimize cell division in mutated CLL and account for prognostic differences. Unifying features of CLL include low responsiveness, expression of CD25, and production of immunosuppressive cytokines. These properties are reminiscent of regulatory T cells and suggest that the cell of origin of CLL might be a regulatory B cell. Continuing regulatory activity, mediated via autoantigen, could suppress Ig production and lead to disease-associated hypogammaglobulinemia.

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Published date: 2004

Identifiers

Local EPrints ID: 26620
URI: http://eprints.soton.ac.uk/id/eprint/26620
ISSN: 0006-4971
PURE UUID: 8c9f5af7-d494-4a8e-9f32-00e4c837f04c
ORCID for F.K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

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Date deposited: 20 Apr 2006
Last modified: 16 Mar 2024 02:54

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Contributors

Author: F.K. Stevenson ORCID iD
Author: F. Caligaris-Cappio

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