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

摘要

AbstractIgD 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 sit