Involvement of CD44 exon v10 in B-cell activation.
The family of CD44 glycoproteins has been suggested to be involved in lymphocyte homing, maturation and activation. Using in vitro blocking studies with a monoclonal antibody, we here addressed the question of functional activity of CD44 variant exon v10 (CD44v10) in B-cell activation. We became interested in this question by the observation that CD44v10O was transiently expressed on activated T cells, B cells and monocytes as well as on a subpopulation of bone marrow cells. A potential ligand, as revealed by staining with a CD44v10 receptor globulin, was only detected on monocytes. Anti-CD44v10 had no major impact on T-cell activation and no influence on primed B cells, but interfered with the mounting of a primary B-cell response to T-independent and T-dependent antigens. Addition of anti-CD44v10 at different stages during the activation process revealed that CD44v10 was not engaged in B-cell-T-cell interactions. The antibody exerted some effect on monocyte activation as defined by a slight decrease in IL-1 production, but most efficiently inhibited antigen-specific as well as mitogen-induced B-cell activation when present during the coculture of virgin B cells with monocytes. These findings, together with the observation that a CD44v10 ligand was only detected on monocytes but not on lymphocytes, point towards a requirement for CD44v10 in a B-cell-monocyte interaction. Furthermore, since activation of B cells by engagement both of the B-cell receptor and of mitogen receptors was inhibited by anti-CD44v10, the data suggest that a costimulatory function of CD44v10 proceeds independent of the B-cell receptor.
Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg.
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M
Rösel
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Föger
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Zöller
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000737:chemistry* / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005091:Exons / Q000502:physiology; D015870:Gene Expression / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000276:immunology; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors