IgD on normal B lymphocytes usually is co-expressed with IgM. A minority of normal plasma cells and rare B cell malignancies express exclusively IgD (IgM-IgD+). The low frequency has been explained by the lack of a recognizable switch region within the C mu-C delta intron. We analyzed four cases of IgM-IgD+ hairy cell leukemia (HCL) by Southern (DNA) blot analysis and identified two cases with a recombinatorial event within the C mu-C delta intron and deletion of C mu. DNA sequence analysis of junctional regions showed that S mu or the immediate upstream region was used as a donor site and that the C mu-C delta intronic sigma delta region was used as acceptor site. Using polymerase chain reaction, we subsequently analyzed whether similar S mu-sigma delta recombinations occur in normal tonsils containing IgM-IgD+ plasma cells. Multiple products with a size range of 200-800 base pairs were detected in all four individuals, suggesting clustering of acceptor sites within sigma delta. Sequence analysis of three cloned products showed S mu-sigma delta recombinations similar those observed in HCL. The sigma delta region contains a relatively high content of pentameric repeats with an extremely G-rich area and appears to function as a vestigial switch recombination site in normal and neoplastic IgM-IgD+ B cells.

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