Non-cell autonomous expression of TNF-alpha-converting enzyme ADAM17 is required for normal lymphocyte development.
TNF-alpha converting enzyme (TACE; ADAM17), a member of the ADAM (a disintegrin and metalloprotease) family of metalloproteases, has been shown to cleave a wide variety of cell surface proteins of immunological importance. Due to the broad expression of TACE and the early postnatal lethality of TACE-deficient mice, it has been difficult to assess the role of TACE in lymphocyte development. Indeed, it is not known whether hemopoietic and/or nonhemopoietic expression of TACE is required for normal lymphocyte development. In the current study, we analyzed the lymphoid system of tace(DeltaZn/DeltaZn) mice and tace(DeltaZn/DeltaZn) bone marrow RAG1(-/-) recipients. Our results clearly show that nonlymphocyte expression of TACE is required for normal lymphocyte development and lymphoid organ structure. Lack of TACE function resulted in a partial block in T cell development at the double-negative 4:double-positive transition in the thymus, a loss of B cell development/maturation in the spleen, and a lack of B cell follicle and germinal center formation in the spleen. Thus, TACE serves as a lymphocyte extrinsic factor that is essential for normal T development and peripheral B cell maturation.
Li
Nianyu
N
Department of Immunology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA.
Boyd
Kelli
K
Dempsey
Peter J
PJ
Vignali
Dario A A
DA
D051722:ADAM Proteins / Q000235:genetics / Q000502:physiology*; D000072198:ADAM17 Protein; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D016026:Bone Marrow Transplantation; D018398:Homeodomain Proteins / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D018398:Homeodomain Proteins; C064658:RAG-1 protein; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606463:Adam17 protein, mouse