CD40 molecules induce down-modulation and endocytosis of T cell surface T cell-B cell activating molecule/CD40-L. Potential role in regulating helper effector function
| Autor: | M J, Yellin, K, Sippel, G, Inghirami, L R, Covey, J J, Lee, J, Sinning, E A, Clark, L, Chess, S, Lederman |
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| Rok vydání: | 1994 |
| Předmět: |
CD4-Positive T-Lymphocytes
B-Lymphocytes Membrane Glycoproteins T-Lymphocytes CD40 Ligand Lymphocyte Cooperation Molecular Sequence Data Temperature Down-Regulation Cell Communication T-Lymphocytes Helper-Inducer In Vitro Techniques Lymphocyte Activation Endocytosis Antigens Differentiation B-Lymphocyte Antigens CD Consensus Sequence Humans Amino Acid Sequence CD40 Antigens Cells Cultured |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 152(2) |
| ISSN: | 0022-1767 |
| Popis: | The T-BAM/CD40-L molecule on CD4+ T cells interacts with B cell CD40 molecules to deliver contact-dependent signals that drive B cell activation and Ig secretion. Cell surface T-BAM/CD40-L expression is transient and may be closely regulated in order to limit the activation and clonal selection of noncognate B cells. We demonstrate that B cells, but not non-B cells, rapidly and specifically down-modulate surface T-BAM/CD40-L expression in a contact-dependent and temperature-sensitive manner that renders T cells unable to activate resting bystander B cells. Because the ability to down-modulate T-BAM/CD40-L correlated with CD40 expression, the role of CD40 molecules in down-modulating its ligand was directly assessed. Anti-CD40 mAb, but not control mAb, block B cell-induced T-BAM/CD40-L down-modulation. Furthermore, CD40+ nonlymphoid transfectants specifically down-modulate surface T-BAM/CD40-L expression. B cells induce T-BAM/CD40-L internalization into cytoplasmic compartments in a process that is inhibited by cytochalasin B. Pretreatment of activated T cells with lysosomotropic agents does not affect CD40-induced down-modulation of surface T-BAM/CD40-L but results in a marked accumulation of T-BAM/CD40-L in cytoplasmic vesicles. Together, these studies strongly suggest that CD40 induced T-BAM/CD40-L down-modulation occurs, in part, by receptor-mediated endocytosis followed by lysosomal degradation and may represent a mechanism to regulate CD4+ T cell helper effector functions. |
| Databáze: | OpenAIRE |
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