IGD CLASS SWITCHING - IDENTIFICATION OF A NOVEL RECOMBINATION SITE INNEOPLASTIC AND NORMAL B-CELLS

IgD on normal B lymphocytes usually is co-expressed with IgM. A minori ty of normal plasma cells and rare B cell malignancies express exclusi vely IgD (IgM(-)-IgD(+)). The low frequency has been explained by the lack of a recognizable switch region within the C mu-C delta intron. W e analyzed four cases of IgM(-)IgD(+) hairy cell leukemia (I-ICL) by S outhern (DNA) blot analysis and identified two cases with a recombinat orial event within the C mu-C delta intron and deletion of C mu. DNA s equence analysis of junctional regions showed that S mu or the immedia te 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 polymeras e 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 pair s were detected in all four individuals, suggesting clustering of acce ptor sites within sigma delta. Sequence analysis of three cloned produ cts showed S mu-sigma delta recombinations similar those observed in H CL. The sigma delta region contains a relatively high content of penta meric 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.