American Association for Cancer Research
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Supplementary Figure Legend from Homing of Human B Cells to Lymphoid Organs and B-Cell Lymphoma Engraftment Are Controlled by Cell Adhesion Molecule JAM-C

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journal contribution
posted on 2023-03-30, 22:06 authored by Carmen Doñate, Christiane Ody, Thomas McKee, Sylvie Ruault-Jungblut, Nicolas Fischer, Patricia Ropraz, Beat A. Imhof, Thomas Matthes

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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. Cancer Res; 73(2); 640–51. ©2012 AACR.