RESUMO
Follicular lymphomas (FLs) localize in lymphoid tissues and recapitulate the structure of normal secondary follicles. The chemokine/chemokine receptor pair CXCL13/CXCR5 is required for the architectural organization of B cells within lymphoid follicles. In this study, we showed that CXCL13 was secreted by FL cells. FL cells expressed CXCR5 and migrated in response to CXCL13. Furthermore, we observed a synergistic effect between CXCL13 and CXCL12 (SDF-1), a chemokine produced by stromal cells in lymphoid tissues. The production of CXCL13 by FL cells and CXCL12 by stromal cells probably directs and participates in the accumulation of FL cells within specific anatomic sites.
Assuntos
Quimiocinas CXC/metabolismo , Quimiotaxia de Leucócito , Linfoma Folicular/metabolismo , Apoptose , Linfócitos B/metabolismo , Linfócitos B/patologia , Ligante de CD40/farmacologia , Células Cultivadas , Quimiocina CXCL13 , Citometria de Fluxo , Humanos , Interleucina-4/farmacologia , Linfoma Folicular/patologia , Receptores CXCR5 , Receptores de Quimiocinas , Receptores de Citocinas/metabolismo , Estimulação Química , Células Tumorais CultivadasRESUMO
Follicular lymphomas (FLs) are neoplastic counterparts of normal germinal center (GC) B cells. FLs are characterized by t(14;18) with deregulation of the Bcl-2 (BCL2) gene. The presence of t(14;18) and overexpression of Bcl-2 is necessary, but not sufficient, to cause this disease. An array containing 588 complementary DNAs (cDNAs) was used to compare the gene expression between GC B cells and FL cells. To specifically monitor genes expressed in normal GC B and FL cells and not the entire tissue compartment, normal and malignant B cells were purified from tissues. Using the array, 37 genes were up-regulated and 28 were down-regulated in FL cells as compared to normal GC B cells. The expression level of each differentially expressed gene was verified by quantitative polymerase chain reaction. Following these studies 24 genes were up-regulated and 8 genes down-regulated with a P value less than.1. Included among the genes that were up-regulated in FLs were cell cycle regulator proteins CDK10, p120, p21CIP1, and p16INK4A; transcription factors/regulators Pax-5 and Id-2, which are involved in normal B-cell development; and genes involved in cell-cell interactions, tumor necrosis factor, interleukin-2R gamma (IL-2R gamma), and IL-4R alpha. Among the genes that were down-regulated in FLs were MRP8 and MRP14, which are involved in adhesion. Interestingly, several of these genes are localized within chromosomal regions already described to be altered in FLs. These findings provide a basis for future studies into the pathogenesis and pathophysiology of FL and may lead to the identification of potential therapeutic targets as well as antigens for immunotherapeutic strategies.
