Chronic hepatitis C virus infection causes B cell lymphoproliferative disorders that include type II mixed cryoglobulinemia and lymphoma. This virus drives the monoclonal expansion and, occasionally, the malignant transformation of B cells producing a polyreactive natural Ab commonly encoded by the V-H(1)-69 variable gene. Owing to their property of producing natural Ab, these cells are reminiscent of murine B-1 and marginal zone B cells. We used anti-Id Abs to track the stages of differentiation and clonal expansion of V-H(1)-69(+) cells in patients with type II mixed cryoglobulinemia. By immunophenotyping and cell size analysis, we could define three discrete stages of differentiation of V(H)1-69(+) B cells: naive (small, IgM(high)IgD(low)CD38(-)CD27(+)CD21(low)CD95(+)CD(5+)), "early memory" (medium-sized, IgM(low)IgD(low) CD38(-)CD27(+)CD21(lo2)CD95(+)CD5(+)) and "late memory" (large-sized, IgM(low) IgM(low-neg)CD38(-)CD27(low)CD21(low-neg)CD5(-)CD95(-)). The B cells expanded in cryoglobulinemia patients have a "memory" phenotype; this fact, together with the evidence for intraclonal variation, suggests that antigenic stimulation by hepatitis C virus causes the unconstrained expansion of activated V(H)1-69(+) B cells. In some cases, these cells replace the entire pool of circulating B cells, although the absolute B cell number remains within normal limits. Absolute monoclonal V(H)1-69+ B lymphocytosis was seen in three patients with cryoglobulinemia and splenic lymphoma; in two of these patients, expanded cells carried trisomy 3q. The data presented here indicate that the hepatitis C virus-driven clonal expansion of memory B cells producing a V(H)1-69(+) natural Ab escapes control mechanisms and subverts B cell homeostasis. Genetic alterations may provide a further growth advantage leading to an overt lymphoproliferative disorder.

Hepatitis C virus drives the unconstrained monoclonal expansion V(H)1-69-expressing memory B cells in type II cryoglobulinemia: A model of infection-driven lymphomagenesis / Carbonari, Maurizio; E., Caprini; Tedesco, Tiziana; F., Mazzetta; V., Tocco; Casato, Milvia; G., Russo; Fiorilli, Massimo. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 174:(2005), pp. 6532-6539.

Hepatitis C virus drives the unconstrained monoclonal expansion V(H)1-69-expressing memory B cells in type II cryoglobulinemia: A model of infection-driven lymphomagenesis

CARBONARI, Maurizio;TEDESCO, tiziana;CASATO, Milvia;FIORILLI, Massimo
2005

Abstract

Chronic hepatitis C virus infection causes B cell lymphoproliferative disorders that include type II mixed cryoglobulinemia and lymphoma. This virus drives the monoclonal expansion and, occasionally, the malignant transformation of B cells producing a polyreactive natural Ab commonly encoded by the V-H(1)-69 variable gene. Owing to their property of producing natural Ab, these cells are reminiscent of murine B-1 and marginal zone B cells. We used anti-Id Abs to track the stages of differentiation and clonal expansion of V-H(1)-69(+) cells in patients with type II mixed cryoglobulinemia. By immunophenotyping and cell size analysis, we could define three discrete stages of differentiation of V(H)1-69(+) B cells: naive (small, IgM(high)IgD(low)CD38(-)CD27(+)CD21(low)CD95(+)CD(5+)), "early memory" (medium-sized, IgM(low)IgD(low) CD38(-)CD27(+)CD21(lo2)CD95(+)CD5(+)) and "late memory" (large-sized, IgM(low) IgM(low-neg)CD38(-)CD27(low)CD21(low-neg)CD5(-)CD95(-)). The B cells expanded in cryoglobulinemia patients have a "memory" phenotype; this fact, together with the evidence for intraclonal variation, suggests that antigenic stimulation by hepatitis C virus causes the unconstrained expansion of activated V(H)1-69(+) B cells. In some cases, these cells replace the entire pool of circulating B cells, although the absolute B cell number remains within normal limits. Absolute monoclonal V(H)1-69+ B lymphocytosis was seen in three patients with cryoglobulinemia and splenic lymphoma; in two of these patients, expanded cells carried trisomy 3q. The data presented here indicate that the hepatitis C virus-driven clonal expansion of memory B cells producing a V(H)1-69(+) natural Ab escapes control mechanisms and subverts B cell homeostasis. Genetic alterations may provide a further growth advantage leading to an overt lymphoproliferative disorder.
2005
01 Pubblicazione su rivista::01a Articolo in rivista
Hepatitis C virus drives the unconstrained monoclonal expansion V(H)1-69-expressing memory B cells in type II cryoglobulinemia: A model of infection-driven lymphomagenesis / Carbonari, Maurizio; E., Caprini; Tedesco, Tiziana; F., Mazzetta; V., Tocco; Casato, Milvia; G., Russo; Fiorilli, Massimo. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 174:(2005), pp. 6532-6539.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/231007
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