Non-redundancy of cytidine deaminases in class switch recombination.
Class switch recombination (CSR), somatic hypermutation, and gene conversion are immunoglobulin diversification mechanisms that are strictly dependent on the activity of the activation-induced cytidine deaminase (AID). The precise role and substrate(s) of AID in these processes remain to be well defined. The closest homologue of AID is APOBEC-1, a bona fide mRNA-editing enzyme, which shares with AID the ability to deaminate cytidines within single-stranded DNA in vitro and in prokaryotic cells. To determine whether APOBEC-1 can therefore substitute for AID in activated B cells, we expressed human AID, a catalytic mutant thereof, and rat APOBEC-1 in AID-deficient murine B cells. Whereas AID rescued CSR, neither the inactive mutant nor APOBEC-1 could complement AID deficiency. This indicates that cytidine deaminase activity is necessary but not sufficient to initiate CSR, and suggests that AID is specifically targeted to its cognate substrate, the immunoglobulin genes or a distinct mRNA, by an as-yet-unknown mechanism.
Fugmann
Sebastian D
SD
Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, USA.
Rush
James S
JS
Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, USA.
Schatz
David G
DG
Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, USA.
D000071479:APOBEC-1 Deaminase; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017578:Immunoglobulin Class Switching; D007134:Immunoglobulin Switch Region; D007700:Kinetics; D051379:Mice; D009154:Mutation; D051381:Rats; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605090:Apobec1 protein, mouse; C000605091:Apobec1 protein, rat; D003564:Cytidine Deaminase