

![]() |
Homing of human B cells to lymphoid organs and B-cell lymphoma engraftment are controlled by cell adhesion molecule JAM-C. |
|
Authors | ||
Published in | Cancer research. 2013, vol. 73, no. 2, p. 640-51 | |
Abstract | 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. | |
Keywords | Adoptive Transfer — Animals — B-Lymphocytes/immunology — Bone Marrow/immunology — Cell Adhesion Molecules/immunology/metabolism/physiology — Cell Movement/immunology — Humans — Lymph Nodes/immunology — Lymphoma, B-Cell/immunology — Mice — Mice, Inbred NOD — Mice, SCID — Spleen/immunology | |
Identifiers | PMID: 23221386 | |
Full text | ||
Structures | ||
Research groups | Analyses cellulaires et moléculaires des hémopathies malignes (929) Lymphomes MALT et réplication virale (807) Molécules d'adhésion et processus de migration cellulaire (167) | |
Citation (ISO format) | DONATE, Carmen et al. Homing of human B cells to lymphoid organs and B-cell lymphoma engraftment are controlled by cell adhesion molecule JAM-C. In: Cancer research, 2013, vol. 73, n° 2, p. 640-51. doi: 10.1158/0008-5472.CAN-12-1756 https://archive-ouverte.unige.ch/unige:28706 |