Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses.
PD-1, an Ig superfamily member, contains an immunoreceptor tyrosine-based inhibitory motif in the cytoplasmic tail. It is expressed in a minor fraction of CD4-CD8- normal thymocytes and induced in peripheral lymphocytes following activation. To assess the possible roles of PD-1 in the immune responses, PD-1-deficient (PD-1-/-) mice were generated by a gene-targeting strategy. PD-1-4- mice developed and grew normally. Although the thymus was apparently normal, PD-1-/- mice showed moderate but consistent splenomegaly, which reflected the increased cellularity of both lymphoid and myeloid cells. The proliferative response of B cells by anti-IgM antibodies, but not of T cells by an anti-CD3 (145-2C11) mAb in vitro, was augmented in PD-1-/- mice as compared with control littermates. PD-1-/- mice showed increased serum levels of IgG2b, IgA and most strikingly IgG3, while those of IgM and IgG1 were comparable with control mice. Furthermore, PD-1-/- mice exhibited significantly augmented IgG3 anti-DNP antibody response to a type 2 T-independent antigen, DNP-Ficoll, with comparable IgM and IgG1 antibody responses with littermate controls. In the peritoneal cavity, the B-1 cell population in PD-1-/- mice exhibited significantly reduced expression of CD5, a negative regulator of B-1 cell activation, despite a marginal increase in the number of B-1 cells. Thus, PD-1 was suggested to be involved in the negative regulation for particular aspects of B cell proliferation and differentiation including class switching.
Nishimura
H
H
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
Minato
N
N
Nakano
T
T
Honjo
T
T
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D017252:CD3 Complex / Q000276:immunology; D018956:CD5 Antigens / Q000096:biosynthesis; D005362:Ficoll / Q000031:analogs & derivatives / Q000494:pharmacology; D018390:Gene Targeting; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects; D007075:Immunoglobulin M / Q000276:immunology; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010529:Peritoneal Cavity / Q000502:physiology; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D013163:Splenomegaly / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D017252:CD3 Complex; D018956:CD5 Antigens; C031007:DNP-Ficoll; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins; D005362:Ficoll