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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2337-2342.
Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-09-3277.


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Submitted September 24, 2003
Accepted November 13, 2003

Monoclonal CD5+ and CD5- B lymphocyte expansions are frequent in the peripheral blood of the elderly

Paolo Ghia*, Giuseppina Prato, Cristina Scielzo, Stefania Stella, Massimo Geuna, Giuseppe Guida, and Federico Caligaris-Cappio

Laboratory of Cancer Immunology, Institute for Cancer Research and Treatment (IRCC), Candiolo, Italy; Department of Oncological Sciences, University of Turin Medical School, Candiolo, Italy; Division of Clinical Immunology and Hematology, Ospedale Mauriziano 'Umberto I', Turin, Italy

* Corresponding author; email: paolo.ghia{at}unito.it.

The responsiveness and diversity of peripheral B-cell repertoire decreases with age, possibly because of B-cell clonal expansions, as suggested by the incidence of serum monoclonal immunoglobulins and of monoclonal Chronic Lymphocytic Leukemia (CLL)-like B-lymphocytes in clinically silent adults. We phenotyped peripheral blood cells from 500 normal subjects >65 years of age with no history nor suspicion of malignancies and no evidence of lymphocytosis. In 19 cases (3.8%) a {kappa}/{lambda} ratio >3:1 or <1:3 was found: 9 were CD5+, CD19+, CD23+, CD20low, CD79blow, sIglow (classic CLL-like phenotype); 3 were CD5+, CD19+, CD23+, CD20high, CD79blow, sIglow (atypical CLL-like) and 7 were CD5-, CD19+, CD20high, CD23-, CD79bbright, FMC7+, sIgbright (non-CLL-like). In two subjects two phenotypically distinct unrelated clones were concomitantly evident. No cases were CD10+. PCR analysis demonstrated a monoclonal rearrangement of IgH genes in 15/19 cases. No bcl-1 nor bcl-2 rearrangements were detected. Using a gating strategy based on CD20/CD5/CD79 expression 13 further CLL-like B-cell clones were identified (cumulative frequency of classic CLL-like 5.5%). Thus phenotypically heterogeneous monoclonal B-lymphocyte expansions are common among healthy elderly and are not limited to classic CLL-like clones but may have the phenotypic features of different chronic lymphoproliferative disorders, involving also CD5- B-cells.


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