Normal and malignant B-cell development with special reference to Hodgkin's disease

1569-8041

germinal center ; Hodgkin's disease ; Ig gene rearrangement ; micromanipulation ; Reed–Sternberg cell ; single-cell PCR

Springer Online Journal Archives 1860-2000

Medicine

Abstract During their development, B lymphocytes are repeatedly selected for theexpression of an appropriate surface receptor: the pre-B-cell receptor atthe pre-B-cell stage and surface immunoglobulin (Ig) at the transition froma pre-B cell to a mature B cell. Furthermore, stringent selection for Bcells expressing high affinity antibodies operates when antigen-activated Bcells proliferate within germinal centers (GC). Here, somatic pointmutations are introduced into rearranged V region genes at a high rate, andB cells acquiring favorable mutations are selected to differentiate intomemory B cells or plasma cells. In the frame of this developmental scheme, extending a recent analysis, weinvestigated 10 primary cases of Hodgkin's disease (HD) for B-lineage originand clonality [1]. Single Hodgkin and Reed–Sternberg (H-RS) cells weremicromanipulated from frozen tissue sections and analyzed by PCR forrearranged V genes. Clonal VH and/orV_κ/V_λ gene rearrangements wereobtained 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 inall clonal VH gene rearrangements. Interestingly, mutationsleading to stop codons in in-frame V gene rearrangements were detected in fourcases. Since GC B cells acquiring such crippling mutations are usuallyefficiently eliminated within the GC, the finding of those mutations indicatesthat H-RS cells are derived from precursors within the GC that escapedapoptosis by a transforming event.

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