IgD class switching: identification of a novel recombination site in neoplastic and normal B cells.
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.
Kluin
P M
PM
Academic Department of Hematology and Cytogenetics, Royal Marsden Hospital, Sutton, GB.
Kayano
H
H
Zani
V J
VJ
Kluin-Nelemans
H C
HC
Tucker
P W
PW
Satterwhite
E
E
Dyer
M J
MJ
D001402:B-Lymphocytes / Q000737:chemistry / Q000145:classification / Q000276:immunology*; D001483:Base Sequence; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics* / Q000276:immunology; D007072:Immunoglobulin D / Q000235:genetics*; D007075:Immunoglobulin M / Q000235:genetics; D016130:Immunophenotyping; D007943:Leukemia, Hairy Cell; D008969:Molecular Sequence Data; D014066:Palatine Tonsil / Q000737:chemistry / Q000276:immunology; D011995:Recombination, Genetic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D007072:Immunoglobulin D; D007075:Immunoglobulin M