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Böttcher, K.* ; Braunschmidt, K.* ; Hirth, G.* ; Schärich, K.* ; Klassert, T.E.* ; Stock, M.* ; Sorgatz, J.* ; Fischer-Burkart, S.* ; Ullrich, S.* ; Frankenberger, S. ; Kritsch, D.* ; Kosan, C.* ; Küppers, R.* ; Strobl, L.J. ; Slevogt, H.* ; Zimber-Strobl, U. ; Jungnickel, B.*

Context-dependent regulation of immunoglobulin mutagenesis by p53.

Mol. Immunol. 138, 128-136 (2021)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
p53 plays a major role in genome maintenance. In addition to multiple p53 functions in the control of DNA repair, a regulation of DNA damage bypass via translesion synthesis has been implied in vitro. Somatic hypermutation of immunoglobulin genes for affinity maturation of antibody responses is based on aberrant translesion polymerase action and must be subject to stringent control to prevent genetic alterations and lymphomagenesis. When studying the role of p53 in somatic hypermutation in vivo, we found altered translesion polymerase-mediated A:T mutagenesis in mice lacking p53 in all organs, but notably not in mice with B cell-specific p53 inactivation, implying that p53 functions in non-B cells may alter mutagenesis in B cells. During class switch recombination, when p53 prevents formation of chromosomal translocations, we in addition detected a B cell-intrinsic role for p53 in altering G:C and A:T mutagenesis. Thus, p53 regulates translesion polymerase activity and shows differential activity during somatic hypermutation versus class switch recombination in vivo. Finally, p53 inhibition leads to increased somatic hypermutation in human B lymphoma cells. We conclude that loss of p53 function may promote genetic instability via multiple routes during antibody diversification in vivo.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Class Switch Recombination ; Germinal Center ; Lymphomagenesis ; P53 ; Somatic Hypermutation ; Translesion Synthesis; Class-switch Recombination; Dna-polymerase-eta; Tumor-suppressor P53; Germinal-center; Somatic Hypermutation; B-cells; Chromosomal Translocations; Gene Hypermutation; Mechanisms; Checkpoint
ISSN (print) / ISBN 0161-5890
e-ISSN 1872-9142
Journal Molecular Immunology
Quellenangaben Volume: 138, Issue: , Pages: 128-136 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
Grants Deutsche Forschungsgemeinschaft (PhD fellowship of the Jena School for Microbial communication)
Deutsche Forschungsgemeinschaft (Heisenberg fellowship)
Collaborative Research Centre/Transregio 124 "FungiNet" (DFG) of the Deutsche Forschungsgemeinschaft
German Federal Ministry of Education and Research
Deutsche Krebshilfe
Deutsche Forschungsgemeinschaft