Hypermutation of immunoglobulin genes in memory B cells of DNA repair-deficient mice.
To investigate the possible involvement of DNA repair in the process of somatic hypermutation of rearranged immunoglobulin variable (V) region genes, we have analyzed the occurrence, frequency, distribution, and pattern of mutations in rearranged Vlambda1 light chain genes from naive and memory B cells in DNA repair-deficient mutant mouse strains. Hypermutation was found unaffected in mice carrying mutations in either of the following DNA repair genes: xeroderma pigmentosum complementation group (XP)A and XPD, Cockayne syndrome complementation group B (CSB), mutS homologue 2 (MSH2), radiation sensitivity 54 (RAD54), poly (ADP-ribose) polymerase (PARP), and 3-alkyladenine DNA-glycosylase (AAG). These results indicate that both subpathways of nucleotide excision repair, global genome repair, and transcription-coupled repair are not required for somatic hypermutation. This appears also to be true for mismatch repair, RAD54-dependent double-strand-break repair, and AAG-mediated base excision repair.
Jacobs
H
H
Basel Institute for Immunology, CH-4005 Basel, Switzerland. jacobs@bii.ch
Fukita
Y
Y
van der Horst
G T
GT
de Boer
J
J
Weeda
G
G
Essers
J
J
de Wind
N
N
Engelward
B P
BP
Samson
L
L
Verbeek
S
S
de Murcia
J M
JM
de Murcia
G
G
te Riele
H
H
Rajewsky
K
K
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004260:DNA Repair / Q000502:physiology*; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D016133:Polymerase Chain Reaction
D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains