title: The trans-chromosomic mouse-derived human monoclonal antibody promotes phagocytosis of Porphyromonas gingivalis by neutrophils.
abstract: BACKGROUND
  As a safe immunotherapeutic approach, human monoclonal antibody (hMAb) may be effective in clearing periodontopathic bacteria. The trans-chromosomic (TC) technology has recently been applied to construction of the TC mouse, which enables us to incorporate entire human chromosome fragments containing immunoglobulin (Ig) gene cluster. The aim of this study is to establish TC mouse-derived hMAb, and to test the in vitro opsonophagocytic activity.
  
  
  METHODS
  Human Ig-producing TC mouse was immunized by recombinant 40-kDa outer membrane protein (r40-kDa OMP) of Porphyromonas gingivalis 381, and the spleen cells were fused with the mouse myeloma cell line. The specificity of antir40- kDa OMP hMAb was evaluated with the enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance assays. Flow cytometric analyses were performed to assess the opsonophagocytic activity.
  
  
  RESULTS
  We successfully constructed 99 IgG isotype clones (IgG1: 84; IgG2: 11; IgG4: four clones), which were specifically reactive with r40-kDa OMP. The anti-r40-kDa OMP IgG1 hMAbs promoted phagocytosis of P. gingivalis by neutrophils. Futhermore, an increased opsonophagocytic activitity of anti-r40-kDa OMP IgG1 hMAbs was observed not only in P. gingivalis 381, but also in the W50, W83, and Su63 strains.
  
  
  CONCLUSIONS
  Our results document the TC mouse-derived hMAb to promote neutrophil phagocytosis of P. gingivalis, suggesting an immunotherapeutic option for clearance of P. gingivalis.
authors.affiliation: Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Takauchi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tahara
authors.forename: Kumiko
authors.initials: K
authors.lastname: Nakazawa
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Shibata
authors.forename: Isao
authors.initials: I
authors.lastname: Ishida
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Abiko
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yoshie
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D051379:Mice; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G