ISSN:
1569-8041
Keywords:
germinal center
;
Hodgkin's disease
;
Ig gene rearrangement
;
micromanipulation
;
Reed–Sternberg cell
;
single-cell PCR
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract During their development, B lymphocytes are repeatedly selected for the expression of an appropriate surface receptor: the pre-B-cell receptor at the pre-B-cell stage and surface immunoglobulin (Ig) at the transition from a pre-B cell to a mature B cell. Furthermore, stringent selection for B cells expressing high affinity antibodies operates when antigen-activated B cells proliferate within germinal centers (GC). Here, somatic point mutations are introduced into rearranged V region genes at a high rate, and B cells acquiring favorable mutations are selected to differentiate into memory B cells or plasma cells. In the frame of this developmental scheme, extending a recent analysis, we investigated 10 primary cases of Hodgkin's disease (HD) for B-lineage origin and clonality [1]. Single Hodgkin and Reed–Sternberg (H-RS) cells were micro manipulated from frozen tissue sections and analyzed by PCR for rearranged V genes. Clonal VH and/orV_κ/V_λ gene rearrangements were obtained from 9 of the cases. This shows that H-RS cells represent a clonal, B-lineage-derived population of tumor cells. Somatic mutations were found in all clonal VH gene rearrangements. Interestingly, mutations leading to stop codons in in-frame V gene rearrangements were detected in four cases. Since GC B cells acquiring such crippling mutations are usually efficiently eliminated within the GC, the finding of those mutations indicates that H-RS cells are derived from precursors within the GC that escaped apoptosis by a transforming event.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008294602841
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