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Internal IgH class switch region deletions are position-independent and enhanced by

Summary: Internal IgH class switch region deletions are
position-independent and enhanced by
AID expression
Darryll D. Dudley*, John P. Manis*, Ali A. Zarrin*, Lianne Kaylor, Ming Tian, and Frederick W. Alt
Howard Hughes Medical Institute, Children's Hospital, Department of Genetics, Harvard Medical School, and Center for Blood Research, Boston, MA 02115
Contributed by Frederick W. Alt, June 4, 2002
Ig heavy chain class switch recombination (CSR) involves a recom-
bination deletion mechanism that exchanges the expressed CH
gene with a downstream CH gene. CSR is mediated by highly
repetitive switch (S) region sequences and requires the activation-
induced deaminase (AID). The S region 5 of the C gene (S ) can
undergo high-frequency internal deletions in normal B cells and B
cell lines activated for CSR, although the relationship of these
deletions and CSR has not been elucidated. In this study, we
introduced constitutively transcribed S or S 2b regions into a
pro-B cell line that can be activated for AID expression, CSR, and
endogenous S deletions. We find that randomly integrated S
region transcription units in these cells also undergo increased
levels of internal rearrangements after cellular activation, indicat-
ing that the deletion process is independent of location within the


Source: Alt,, Frederick - Immune Disease Institute, Harvard University


Collections: Biology and Medicine