IgD class switching: Identification of a novel recombination site in neoplastic and normal B cells

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Abstract
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 Cμ-Cδ 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 Cμ-Cδ intron and deletion of Cμ. DNA sequence analysis of junctional regions showed that Sμ or the immediate upstream region was used as a donor site and that the Cμ-Cδ intronic σδ region was used as acceptor site. Using polymerase chain reaction, we subsequently analyzed whether similar Sμ-σδ 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 σδ. Sequence analysis of three cloned products showed Sμ-σδ recombinations similar those observed in HCL. The σδ 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.