Poly(ADP-ribose) polymerase-1 (Parp-1)-deficient mice demonstrate abnormal antibody responses.
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.
Ambrose
Helen E
HE
Department of Haematology, Imperial College London, UK.
Willimott
Shaun
S
Beswick
Richard W
RW
Dantzer
Françoise
F
de Murcia
Josiane Ménissier
JM
Yelamos
José
J
Wagner
Simon D
SD
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018858:Germinal Center / Q000276:immunology; D007114:Immunization; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007136:Immunoglobulins / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008211:Lymphocyte Cooperation / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D007136:Immunoglobulins; D008070:Lipopolysaccharides; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
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