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Title

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

Authors
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
Identifiers
PMID: 23221386
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Structures
Research groups Lymphomes MALT et réplication virale (807)
Molécules d'adhésion et processus de migration cellulaire (167)
Analyses cellulaires et moléculaires des hémopathies malignes (929)
Citation
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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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