Anti-CD20 treatment depletes B-cells in blood and lymphatic tissue of cynomolgus monkeys

Carsten Schröder, Agnes M. Azimzadeh, Guosheng Wu, James O. Price, James B. Atkinson, Richard N. Pierson

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

Introduction: Macaque species offer a valuable model for translational allo-transplantation and tolerance studies. Cardiac allograft vasculopathy in Macaca fascicularis is associated with elaboration of anti-donor antibodies. Since T-independent pathways of B cell activation have been described, and anti-B cell strategies have proven to be a fruitful tolerogenic adjunct in rodent and xenogenic models, here we investigate whether an anti-CD20 antibody (rituximab) would be useful to deplete B-cells in a pre-clinical allo-transplantation setting in macaques. Methods: Three cynomolgus macaques which had previously rejected a cardiac allograft and one with concurrent subacute vascular rejection were treated weekly with rituximab 20 mg/kg IV for 4 and 2 weeks, respectively. B-cell levels (CD19+ cells) were measured by flow cytometry in peripheral blood, spleen, lymph node and bone marrow cells at various intervals after initiation of treatment. B-cells and plasma cells were also analyzed by immunohisto-chemistry at necropsy in spleen, lymph node, tonsil and thymus tissue sections. Anti-donor antibody liters were measured by flow cytometry. Results: B-cells expressing CD19 were not detectable in the peripheral blood in any animal within 24 h after initial treatment, or over the ensuing month. At necropsy, the germinal centers in spleen and lymph node were completely depleted of CD20+ B-cells in 2 animals, leaving a hypocellular trabecular pattern around preserved plasma cell follicles. Substantial but incomplete depletion of B-cells was demonstrated in the other 2 animals, in each instance immunohistochemical findings in spleen and lymph node exhibiting higher sensitivity for residual B-cells compared to FACS. Anti-donor antibody tilers exhibited kinetics similar to untreated animals over this short follow-up. Comment: Treatment with anti-CD20 very efficiently depletes peripheral and tissue B-cells but not plasma cells in this macaque species. Biopsy of lymph node is necessary and may be sufficient to assess B-cell clearance in secondary lymphoid organs in this model.

Original languageEnglish (US)
Pages (from-to)19-28
Number of pages10
JournalTransplant Immunology
Volume12
Issue number1
DOIs
StatePublished - Oct 1 2003

Keywords

  • Allo-antibodies
  • Anti-CD20 therapy
  • B-cell depletion
  • Non-human primate
  • Plasma cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Transplantation

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    Schröder, C., Azimzadeh, A. M., Wu, G., Price, J. O., Atkinson, J. B., & Pierson, R. N. (2003). Anti-CD20 treatment depletes B-cells in blood and lymphatic tissue of cynomolgus monkeys. Transplant Immunology, 12(1), 19-28. https://doi.org/10.1016/S0966-3274(03)00059-5