Non-cell autonomous expression of TNF-alpha-converting enzyme ADAM17 is required for normal lymphocyte development

J Immunol. 2007 Apr 1;178(7):4214-21. doi: 10.4049/jimmunol.178.7.4214.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / physiology*
  • ADAM17 Protein
  • Animals
  • B-Lymphocytes / immunology*
  • Bone Marrow Transplantation
  • Homeodomain Proteins / genetics
  • Lymphocyte Activation* / genetics
  • Mice
  • Mice, Mutant Strains
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes / immunology*


  • Homeodomain Proteins
  • RAG-1 protein
  • ADAM Proteins
  • ADAM17 Protein
  • Adam17 protein, mouse