Activation-induced deaminase (AID)-directed hypermutation in the immunoglobulin Sμ region: implication of AID involvement in a common step of class switch …

H Nagaoka, M Muramatsu, N Yamamura… - The Journal of …, 2002 - rupress.org
H Nagaoka, M Muramatsu, N Yamamura, K Kinoshita, T Honjo
The Journal of experimental medicine, 2002rupress.org
Somatic hypermutation (SHM) and class switch recombination (CSR) cause distinct genetic
alterations at different regions of immunoglobulin genes in B lymphocytes: point mutations in
variable regions and large deletions in S regions, respectively. Yet both depend on
activation-induced deaminase (AID), the function of which in the two reactions has been an
enigma. Here we report that B cell stimulation which induces CSR but not SHM, leads to AID-
dependent accumulation of SHM-like point mutations in the switch μ region, uncoupled with …
Somatic hypermutation (SHM) and class switch recombination (CSR) cause distinct genetic alterations at different regions of immunoglobulin genes in B lymphocytes: point mutations in variable regions and large deletions in S regions, respectively. Yet both depend on activation-induced deaminase (AID), the function of which in the two reactions has been an enigma. Here we report that B cell stimulation which induces CSR but not SHM, leads to AID-dependent accumulation of SHM-like point mutations in the switch μ region, uncoupled with CSR. These findings strongly suggest that AID itself or a single molecule generated by RNA editing function of AID may mediate a common step of SHM and CSR, which is likely to be involved in DNA cleavage.
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