Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses

Int Immunol. 1998 Oct;10(10):1563-72. doi: 10.1093/intimm/10.10.1563.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Antigens, Surface*
  • Apoptosis Regulatory Proteins
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Bone Marrow Cells / cytology
  • CD3 Complex / immunology
  • CD5 Antigens / biosynthesis
  • Ficoll / analogs & derivatives
  • Ficoll / pharmacology
  • Gene Targeting
  • Immunoglobulin G / blood
  • Immunoglobulin G / drug effects
  • Immunoglobulin M / immunology
  • Leukocyte Count
  • Lymphocyte Activation / drug effects
  • Lymphocyte Count
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peritoneal Cavity / physiology
  • Programmed Cell Death 1 Receptor
  • Proteins / genetics*
  • Proteins / physiology*
  • Spleen / cytology
  • Splenomegaly / immunology
  • T-Lymphocytes / immunology


  • Antibodies
  • Antibodies, Monoclonal
  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • CD3 Complex
  • CD5 Antigens
  • DNP-Ficoll
  • Immunoglobulin G
  • Immunoglobulin M
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Proteins
  • Ficoll