Immunoglobulin D Switching Can Occur through Homologous Recombination in Human Β Cells

MB White, CJ Word, CG Humphries… - … and cellular biology, 1990 - Am Soc Microbiol
MB White, CJ Word, CG Humphries, FR Blattner, PW Tucker
Molecular and cellular biology, 1990Am Soc Microbiol
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 δ. Deletion of C μ 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 Β lymphocytes, an IgD switch can occur through homologous recombination of a …
Abstract
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 (C H) except C δ. Deletion of C μ 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 Β 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 J H complex and a 443-bp sequence that is duplicated almost perfectly (96% similarity) 1.7 kbp 5'of the C δ gene (442/443-base-pair [bp] repeat). This homologous recombination mechanism is not exclusive for IgD switching, since C μ 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.
American Society for Microbiology