Homing of Human B Cells to Lymphoid Organs and B-Cell Lymphoma Engraftment Are Controlled by Cell Adhesion Molecule JAM-C

• Published in: Cancer research (Chicago, Ill.) Vol. 73; no. 2; pp. 640 - 651
• Main Authors: DONATE, Carmen, ODY, Christiane, MCKEE, Thomas, RUAULT-JUNGBLUT, Sylvie, FISCHER, Nicolas, ROPRAZ, Patricia, IMHOF, Beat A, MATTHES, Thomas
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.01.2013
• Subjects: Adoptive Transfer; Animals; Antineoplastic agents; B-Lymphocytes - immunology; Biological and medical sciences; Bone Marrow - immunology; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - metabolism; Cell Adhesion Molecules - physiology; Cell Movement - immunology; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymph Nodes - immunology; Lymphoma, B-Cell - immunology; Medical sciences; Mice; Mice, Inbred NOD; Mice, SCID; Pharmacology. Drug treatments; Spleen - immunology; Tumors; Human; Junctional adhesion molecule C; Lymphoid cell; Lymphoid organ; Lymphoproliferative syndrome; Cell adhesion molecule; Engraftment; Homing phenomenon; Malignant hemopathy; B-Lymphocyte; Lymphoma; Cancer
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-12-1756

Junctional adhesion molecule C (JAM-C) is expressed by vascular endothelium and human but not mouse B lymphocytes. The level of JAM-C expression defines B-cell differentiation stages and allows the classification of marginal zone-derived (JAM-C-positive) and germinal center-derived (JAM-C-negative) B-cell lymphomas. In the present study, we investigated the role of JAM-C in homing of human B cells, using a xenogeneic nonobese diabetic/severe combined immunodeficient mouse model. Treatment with anti-JAM-C antibodies in short-term experiments reduced migration of normal and malignant JAM-C-expressing B cells to bone marrow, lymph nodes, and spleen. Blocking homing to the spleen is remarkable, as most other antiadhesion antibodies reduce homing of B cells only to bone marrow and lymph nodes. Long-term administration of anti-JAM-C antibodies prevented engraftment of JAM-Cpos lymphoma cells in bone marrow, spleen, and lymph nodes of mice. Plasmon resonance studies identified JAM-B as the major ligand for JAM-C, whereas homotypic JAM-C interactions remained at background levels. Accordingly, anti-JAM-C antibodies blocked adhesion of JAM-C-expressing B cells to their ligand JAM-B, and immunofluorescence analysis showed the expression of JAM-B on murine and human lymphatic endothelial cells. Targeting JAM-C could thus constitute a new therapeutic strategy to prevent lymphoma cells from reaching supportive microenvironments not only in the bone marrow and lymph nodes but also in the spleen.