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Homing of human B cells to lymphoid organs and B-cell lymphoma engraftment are controlled by cell adhesion molecule JAM-C.

Ruault-Jungblut, Sylvie
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 TransferAnimalsB-Lymphocytes/immunologyBone Marrow/immunologyCell Adhesion Molecules/immunology/metabolism/physiologyCell Movement/immunologyHumansLymph Nodes/immunologyLymphoma, B-Cell/immunologyMiceMice, Inbred NODMice, SCIDSpleen/immunology
PMID: 23221386
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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)
(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

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Deposited on : 2013-06-26

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