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Poly(ADP‐ribose) polymerase‐1 (Parp‐1)‐deficient mice demonstrate abnormal antibody responses
Author(s) -
Ambrose Helen E.,
Willimott Shaun,
Beswick Richard W.,
Dantzer Françoise,
De Murcia Josiane Ménissier,
Yelamos José,
Wagner Simon D.
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02921.x
Subject(s) - immunoglobulin class switching , isotype , biology , microbiology and biotechnology , poly adp ribose polymerase , antibody , germinal center , b cell , polymerase , immunology , dna , monoclonal antibody , genetics
Summary Poly(ADP‐ribosylation) of acceptor proteins is an epigenetic modification involved in DNA strand break repair, recombination and transcription. Here we provide evidence for the involvement of poly(ADP‐ribose) polymerase‐1 (Parp‐1) in antibody responses. Parp‐1 − /− mice had increased numbers of T cells and normal numbers of total B cells. Marginal zone B cells were mildly reduced in number, and numbers of follicular B cells were preserved. There were abnormal levels of basal immunoglobulins, with reduced levels of immunoglobulin G2a (IgG2a) and increased levels of IgA and IgG2b. Analysis of specific antibody responses showed that T cell‐independent responses were normal but T cell‐dependent responses were markedly reduced. Germinal centres were normal in size and number. In vitro purified B cells from Parp‐1 −/− mice proliferated normally and showed normal IgM secretion, decreased switching to IgG2a but increased IgA secretion. Collectively our results demonstrate that Parp‐1 has essential roles in normal T cell‐dependent antibody responses and the regulation of isotype expression. We speculate that Parp‐1 forms a component of the protein complex involved in resolving the DNA double‐strand breaks that occur during class switch recombination.