Ig gene diversification and selection in follicular lymphoma, diffuse large B cell lymphoma and primary central nervous system lymphoma revealed by lineage tree and mutation analyses.
Int Immunol
; 22(11): 875-87, 2010 Nov.
Article
en En
| MEDLINE
| ID: mdl-21059768
ABSTRACT
Follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL) and primary central nervous system lymphoma are B cell malignancies. FL and DLBCL have a germinal center origin. We have applied mutational analyses and a novel algorithm for quantifying shape properties of mutational lineage trees to investigate the nature of the diversification, somatic hypermutation and selection processes that affect B cell clones in these malignancies and reveal whether they differ from normal responses. Lineage tree analysis demonstrated higher diversification and mutations per cell in the lymphoma clones. This was caused solely by the longer diversification times of the malignant clones, as their recent diversification processes were similar to those of normal responses, implying similar mutation frequencies. Since previous analyses of antigen-driven selection were shown to yield false positives, we performed a corrected analysis of replacement and silent mutation patterns, which revealed selection against replacement mutations in the framework regions, responsible for the structural integrity of the B cell receptor, but not for positive selection for replacements in the complementary determining regions. Most replacements, however, were neutral or conservative, suggesting that if at all selection operates in these malignancies it is for structural B cell receptor integrity but not for antigen binding.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Análisis Mutacional de ADN
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Genes de Inmunoglobulinas
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Linfoma Folicular
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Linfoma de Células B Grandes Difuso
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Neoplasias del Sistema Nervioso Central
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Linaje de la Célula
Límite:
Humans
Idioma:
En
Revista:
Int Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Israel