Chronic lymphocytic leukemia

Revelations from the B-cell receptor

Freda K. Stevenson, Federico Caligaris-Cappio

Research output: Contribution to journalArticle

316 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4389-4395
Number of pages7
JournalBlood
Volume103
Issue number12
DOIs
Publication statusPublished - Jun 15 2004

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
Cells
Aptitude
Genes
Immunoglobulin Variable Region
Regulatory B-Lymphocytes
B-Lymphocytes
Antigens
T-cells
Autoantigens
Agammaglobulinemia
Immunosuppressive Agents
Germinal Center
Regulatory T-Lymphocytes
Immunoglobulins
Tumors
Blood
Cell Division
Mental Competency
Blood Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Chronic lymphocytic leukemia : Revelations from the B-cell receptor. / Stevenson, Freda K.; Caligaris-Cappio, Federico.

In: Blood, Vol. 103, No. 12, 15.06.2004, p. 4389-4395.

Research output: Contribution to journalArticle

Stevenson, FK & Caligaris-Cappio, F 2004, 'Chronic lymphocytic leukemia: Revelations from the B-cell receptor', Blood, vol. 103, no. 12, pp. 4389-4395. https://doi.org/10.1182/blood-2003-12-4312
Stevenson, Freda K. ; Caligaris-Cappio, Federico. / Chronic lymphocytic leukemia : Revelations from the B-cell receptor. In: Blood. 2004 ; Vol. 103, No. 12. pp. 4389-4395.
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