Immunoglobulin D switching can occur through homologous recombination in human B cells.
Prototypical class switching in mouse and human immunoglobulin heavy chains occurs through recombination of tandem blocks of short repeats located 5' to each heavy chain constant region (CH) except C delta. Deletion of C mu in immunoglobulin D (IgD)-secreting murine plasmacytomas occurs illegitimately. We demonstrate here that in human IgD-secreting myeloma cells freshly isolated from patient bone marrow and in normal peripheral blood B lymphocytes, an IgD switch can occur through homologous recombination of a direct repeat consisting of a 442-bp sequence 1.5 kbp 3' of the JH complex and a 443-bp sequence that is duplicated almost perfectly (96% similarity) 1.7 kbp 5' of the C delta gene (442/443-base-pair [bp] repeat). This homologous recombination mechanism is not exclusive for IgD switching, since C mu deletion endpoints in two established IgD-secreting myeloma cell lines fall outside the 442/443-bp repeat. The 442/443-bp mediated recombination shows cell type specificity, and we propose that it represents a unique mode for increased levels of IgD secretion in humans.
White
M B
MB
Department of Genetics, University of Wisconsin, Madison 53706.
Word
C J
CJ
Humphries
C G
CG
Blattner
F R
FR
Tucker
P W
PW
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D002872:Chromosome Deletion; D004273:DNA, Neoplasm / Q000235:genetics; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D015698:Genomic Library; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007072:Immunoglobulin D / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010954:Plasmacytoma / Q000276:immunology; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic
D004273:DNA, Neoplasm; D007127:Immunoglobulin Constant Regions; D007072:Immunoglobulin D; D007143:Immunoglobulin Heavy Chains; D015345:Oligonucleotide Probes