title: Homing of human B cells to lymphoid organs and B-cell lymphoma engraftment are controlled by cell adhesion molecule JAM-C.
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.
authors.affiliation: Hematology Service, University Hospital, Geneva, Switzerland.
authors.forename: Carmen
authors.initials: C
authors.lastname: Doñate
authors.forename: Christiane
authors.initials: C
authors.lastname: Ody
authors.forename: Thomas
authors.initials: T
authors.lastname: McKee
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ruault-Jungblut
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fischer
authors.forename: Patricia
authors.initials: P
authors.lastname: Ropraz
authors.forename: Beat A
authors.initials: BA
authors.lastname: Imhof
authors.forename: Thomas
authors.initials: T
authors.lastname: Matthes
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013154:Spleen / Q000276:immunology; D062765:Junctional Adhesion Molecule B
chemical_list: D015815:Cell Adhesion Molecules; C448000:JAM3 protein, human; C498781:Jam2 protein, mouse; D062765:Junctional Adhesion Molecule B