title: CD47 limits antibody dependent phagocytosis against non-malignant B cells.
abstract: Recent studies have demonstrated the importance of CD47 in protecting malignant B cells from antibody dependent cellular phagocytosis (ADCP). Combined treatment of anti-CD47 and -CD20 antibodies synergistically augment elimination of tumor B cells in xenograft mouse models. This has led to the development of novel reagents that can potentially enhance killing of malignant B cells in patients. B cell depleting therapy is also a promising treatment for autoimmune patients. In the current study, we aimed to investigate whether or not CD47 protects non-malignant B cells from ADCP. We show that CD47 is expressed on all B cells in mice, with the highest level on plasma cells in bone marrow and spleen. Although its expression is dispensable for B cell development in mice, CD47 on B cells limits antibody mediated phagocytosis. B cell depletion following in vivo anti-CD19 treatment is more efficient in CD47-/- mice than in wild type mice. In vitro, both naïve and activated B cells from CD47-/- mice are more sensitive to ADCP than wild type B cells. Lastly, we show in an ADCP assay that blocking CD47 can enhance anti-CD19 antibody mediated phagocytosis of wild type B cells. These results suggest that in addition to its already demonstrated benefit in cancer, targeting CD47 may be used as an adjunct in combination with B cell depletion antibodies for treatment of autoimmune diseases.
authors.affiliation: Department of Oncology Research, MedImmune, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gallagher
authors.affiliation: Department of Oncology Research, MedImmune, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Turman
authors.affiliation: Department of Protein Science, MedImmune, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Lekstrom
authors.affiliation: Department of Protein Science, MedImmune, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Wilson
authors.affiliation: Department of Oncology Research, MedImmune, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Herbst
authors.affiliation: Department of Oncology Research, MedImmune, One MedImmune Way, Gaithersburg, MD 20878, USA. Electronic address: wangy@medimmune.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D051928:CD47 Antigen / Q000276:immunology*; D049109:Cell Proliferation; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis / Q000276:immunology*
chemical_list: D051928:CD47 Antigen; C497895:Cd47 protein, mouse
keywords: Antibody mediated phagocytosis; Antibody therapy; B cell depletion; CD19; CD47; Knockout mice