ArticleJournal of immunology (Baltimore, Md. : 1950)1999
Induction of Ig somatic hypermutation and class switching in a human monoclonal IgM+ IgD+ B cell line in vitro: definition of the requirements and modalities of hypermutation.
Article in Journal of immunology (Baltimore, Md. : 1950), 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 94 citations in OpenAlex.
- Article
- Expression of Constitutive Fusion of Ubiquitin to PCNA Restores the Level of Immunoglobulin A/T Mutations During Somatic Hypermutation in the Ramos Cell Line.Frontiers in immunology · 2022Article
- Insights Into the Structure-Function Relationships of Dimeric C3d Fragments.Frontiers in immunology · 2021Article
- Rev1 recruits ung to switch regions and enhances du glycosylation for immunoglobulin class switch DNA recombination.Cell reports · 2012Article
- HoxC4 binds to the promoter of the cytidine deaminase AID gene to induce AID expression, class-switch DNA recombination and somatic hypermutation.Nature immunology · 2009Article
- Article
- AID- and Ung-dependent generation of staggered double-strand DNA breaks in immunoglobulin class switch DNA recombination: a post-cleavage role for AID.Molecular immunology · 2008Article
- Evolution of ADAMTS13 antibodies in a fatal case of thrombotic thrombocytopenic purpura.American journal of hematology · 2008Article
- A/T mutagenesis in hypermutated immunoglobulin genes strongly depends on PCNAK164 modification.The Journal of experimental medicine · 2007Article
- DNA replication to aid somatic hypermutation.Advances in experimental medicine and biology · 2007Review
- Regulation of aicda expression and AID activity: relevance to somatic hypermutation and class switch DNA recombination.Critical reviews in immunology · 2007Review
- DNA repair in antibody somatic hypermutation.Trends in immunology · 2006Review
- AID-dependent histone acetylation is detected in immunoglobulin S regions.The Journal of experimental medicine · 2006Article
- The translesion DNA polymerase theta plays a dominant role in immunoglobulin gene somatic hypermutation.The EMBO journal · 2005Article
- DNA lesions and repair in immunoglobulin class switch recombination and somatic hypermutation.Annals of the New York Academy of Sciences · 2005Review
- Activation-induced cytidine deaminase expression in follicular lymphoma: association between AID expression and ongoing mutation in FL.Leukemia · 2004Article
- Immunoglobulin somatic hypermutation: double-strand DNA breaks, AID and error-prone DNA repair.Journal of clinical immunology · 2003Review
- AID-dependent generation of resected double-strand DNA breaks and recruitment of Rad52/Rad51 in somatic hypermutation.Immunity · 2003Article
- Class-switch recombination: after the dawn of AID.Current opinion in immunology · 2003Review
- Transcript expression of two Iglambda rearrangements and RAG-1/RAG-2 in a mature human B cell producing IgMlambda islet cell autoantibody.Journal of clinical immunology · 2003Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Partly because of the lack of a suitable in vitro model, the trigger(s) and the mechanism(s) of somatic hypermutation in Ig genes are largely unknown. We have analyzed the hypermutation potential of human CL-01 lymphocytes, our monoclonal model of germinal center B cell differentiation. These cells are surface IgM+ IgD+ and, in the absence of T cells, switch to IgG, IgA, and IgE in response to CD40:CD40 ligand engagement and exposure to appropriate cytokines. We show here that CL-01 cells can be induced to effectively mutate the expressed VHDJH-C mu, VHDJH-C delta, VHDJH-C gamma, VHDJH-C alpha, VHDJH-C epsilon, and V lambda J lambda-C lambda transcripts before and after Ig class switching in a stepwise fashion. In these cells, induction of somatic mutations required cross-linking of the surface receptor for Ag and T cell contact through CD40:CD40 ligand and CD80: CD28 coengagement. The induced mutations showed intrinsic features of Ig V(D)J hypermutation in that they comprised 110 base substitutions (97 in the heavy chain and 13 in the lambda-chain) and only 2 deletions and targeted V(D)J, virtually sparing CH and C lambda. These mutations were more abundant in secondary VHDJH-C gamma than primary VHDJH-C mu transcripts and in V(D)J-C than V lambda J lambda-C lambda transcripts. These mutations were also associated with coding DNA strand polarity and showed an overall rate of 2.42 x 10(-4) base changes/cell division in VHDJH-CH transcripts. Transitions were favored over transversions, and G nucleotides were preferentially targeted, mainly in the context of AG dinucleotides. Thus, in CL-01 cells, Ig somatic hypermutation is readily inducible by stimuli different from those required for class switching and displays discrete base substitution modalities.
Indexed as
Identifiers
10092799PMC4623562W1633281553What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.