Tumor cell dissemination in follicular lymphoma.
The derivation of follicular lymphomas (FLs) from germinal centers is not only supported by their morphologic appearance with a nodular growth pattern and a germinal center-like cellular composition, but also by the presence of ongoing somatic hypermutation (a germinal center B cell-specific process) during their clonal expansion. The intraclonal sequence diversity of the tumor cells and their follicular growth pattern allows one to analyze lymphoma cell dissemination and the way the tumor "metastasizes" to distinct follicles. In the present study, we analyzed individual follicles of 3 FLs by micromanipulation of single cells from individual lymphoma follicles and amplification of immunoglobulin V region genes. Genealogical trees for the V(H) and the V(L) gene rearrangements were constructed to analyze the clonal relationship among individual cells of 3 distinct follicles of each case. In all 3 cases there is evidence that distinct tumor follicles are founded by many tumor cells, suggesting that there is extensive migration of the tumor cells among follicles. The observation that the tumor cells of FLs retain their follicular growth patterns despite this cellular migration supports the idea that they depend on the follicular microenvironment for their clonal expansion.
Oeschger
Sabine
S
Senckenberg Department of Pathology, University of Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. oeschger@em.uni-frankfurt.de
Bräuninger
Andreas
A
Küppers
Ralf
R
Hansmann
Martin-Leo
ML
D002465:Cell Movement; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D015321:Gene Rearrangement; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000032:analysis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000032:analysis / Q000235:genetics; D008198:Lymph Nodes / Q000473:pathology; D008224:Lymphoma, Follicular / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region