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. 1997 Jul 16;16(14):4217–4225. doi: 10.1093/emboj/16.14.4217

Normal development but differentially altered proliferative responses of lymphocytes in mice lacking CD81.

T Miyazaki 1, U Müller 1, K S Campbell 1
PMCID: PMC1170047  PMID: 9250665

Abstract

CD81 (TAPA-1) is a member of the transmembrane 4 superfamily (TM4SF) which is expressed on the cell surface of most cells of the body throughout their cellular differentiation. It has been recognized in several cell surface complexes of lymphocytes, suggesting that it may have diverse roles in lymphocyte development and activation regulation. Mice with a CD81 null mutation revealed normal T- and conventional B-cell development, although CD19 expression on B cells was dull and B-1 cells were reduced in number. However, both T and B cells of mutant mice exhibited strikingly enhanced proliferation in response to various types of stimuli. Interestingly, while proliferative responses of T cells following T-cell antigen receptor (TCR) engagement was enhanced in the absence of CD81, B-cell proliferation in response to B-cell antigen-receptor (BCR) cross-linking was severely impaired. Despite these altered proliferative responses, both tyrosine phosphorylation and intracellular calcium flux in response to cross-linking of cell surface antigen receptors were normal in mutant mice, reflecting apparently normal initial signaling of antigen receptors. In conclusion, though CD81 is not essential for normal T- and conventional B-cell development, it plays key roles in controlling lymphocyte homeostasis by regulating lymphocyte proliferation in distinct manners, dependent on the context of stimulation.

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Selected References

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  1. Boismenu R., Rhein M., Fischer W. H., Havran W. L. A role for CD81 in early T cell development. Science. 1996 Jan 12;271(5246):198–200. doi: 10.1126/science.271.5246.198. [DOI] [PubMed] [Google Scholar]
  2. Bradbury L. E., Kansas G. S., Levy S., Evans R. L., Tedder T. F. The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules. J Immunol. 1992 Nov 1;149(9):2841–2850. [PubMed] [Google Scholar]
  3. Campbell K. S., Dessing M., Lopez-Botet M., Cella M., Colonna M. Tyrosine phosphorylation of a human killer inhibitory receptor recruits protein tyrosine phosphatase 1C. J Exp Med. 1996 Jul 1;184(1):93–100. doi: 10.1084/jem.184.1.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carter R. H., Fearon D. T. CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science. 1992 Apr 3;256(5053):105–107. doi: 10.1126/science.1373518. [DOI] [PubMed] [Google Scholar]
  5. Engel P., Zhou L. J., Ord D. C., Sato S., Koller B., Tedder T. F. Abnormal B lymphocyte development, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule. Immunity. 1995 Jul;3(1):39–50. doi: 10.1016/1074-7613(95)90157-4. [DOI] [PubMed] [Google Scholar]
  6. Fearon D. T. The CD19-CR2-TAPA-1 complex, CD45 and signaling by the antigen receptor of B lymphocytes. Curr Opin Immunol. 1993 Jun;5(3):341–348. doi: 10.1016/0952-7915(93)90051-s. [DOI] [PubMed] [Google Scholar]
  7. Hardy R. R., Hayakawa K. CD5 B cells, a fetal B cell lineage. Adv Immunol. 1994;55:297–339. doi: 10.1016/s0065-2776(08)60512-x. [DOI] [PubMed] [Google Scholar]
  8. Kisielow P., Blüthmann H., Staerz U. D., Steinmetz M., von Boehmer H. Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature. 1988 Jun 23;333(6175):742–746. doi: 10.1038/333742a0. [DOI] [PubMed] [Google Scholar]
  9. Le Meur M., Gerlinger P., Benoist C., Mathis D. Correcting an immune-response deficiency by creating E alpha gene transgenic mice. Nature. 1985 Jul 4;316(6023):38–42. doi: 10.1038/316038a0. [DOI] [PubMed] [Google Scholar]
  10. Matsumoto A. K., Kopicky-Burd J., Carter R. H., Tuveson D. A., Tedder T. F., Fearon D. T. Intersection of the complement and immune systems: a signal transduction complex of the B lymphocyte-containing complement receptor type 2 and CD19. J Exp Med. 1991 Jan 1;173(1):55–64. doi: 10.1084/jem.173.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Miyazaki T., Dierich A., Benoist C., Mathis D. Independent modes of natural killing distinguished in mice lacking Lag3. Science. 1996 Apr 19;272(5260):405–408. doi: 10.1126/science.272.5260.405. [DOI] [PubMed] [Google Scholar]
  12. Miyazaki T., Wolf P., Tourne S., Waltzinger C., Dierich A., Barois N., Ploegh H., Benoist C., Mathis D. Mice lacking H2-M complexes, enigmatic elements of the MHC class II peptide-loading pathway. Cell. 1996 Feb 23;84(4):531–541. doi: 10.1016/s0092-8674(00)81029-6. [DOI] [PubMed] [Google Scholar]
  13. Nagira M., Imai T., Ishikawa I., Uwabe K. I., Yoshie O. Mouse homologue of C33 antigen (CD82), a member of the transmembrane 4 superfamily: complementary DNA, genomic structure, and expression. Cell Immunol. 1994 Aug;157(1):144–157. doi: 10.1006/cimm.1994.1212. [DOI] [PubMed] [Google Scholar]
  14. Oren R., Takahashi S., Doss C., Levy R., Levy S. TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins. Mol Cell Biol. 1990 Aug;10(8):4007–4015. doi: 10.1128/mcb.10.8.4007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rickert R. C., Rajewsky K., Roes J. Impairment of T-cell-dependent B-cell responses and B-1 cell development in CD19-deficient mice. Nature. 1995 Jul 27;376(6538):352–355. doi: 10.1038/376352a0. [DOI] [PubMed] [Google Scholar]
  16. Robey E., Allison J. P. T-cell activation: integration of signals from the antigen receptor and costimulatory molecules. Immunol Today. 1995 Jul;16(7):306–310. doi: 10.1016/0167-5699(95)80140-5. [DOI] [PubMed] [Google Scholar]
  17. Rodewald H. R., Awad K., Moingeon P., D'Adamio L., Rabinowitz D., Shinkai Y., Alt F. W., Reinherz E. L. Fc gamma RII/III and CD2 expression mark distinct subpopulations of immature CD4-CD8- murine thymocytes: in vivo developmental kinetics and T cell receptor beta chain rearrangement status. J Exp Med. 1993 Apr 1;177(4):1079–1092. doi: 10.1084/jem.177.4.1079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rubinstein E., Le Naour F., Lagaudrière-Gesbert C., Billard M., Conjeaud H., Boucheix C. CD9, CD63, CD81, and CD82 are components of a surface tetraspan network connected to HLA-DR and VLA integrins. Eur J Immunol. 1996 Nov;26(11):2657–2665. doi: 10.1002/eji.1830261117. [DOI] [PubMed] [Google Scholar]
  19. Szöllósi J., Horejsí V., Bene L., Angelisová P., Damjanovich S. Supramolecular complexes of MHC class I, MHC class II, CD20, and tetraspan molecules (CD53, CD81, and CD82) at the surface of a B cell line JY. J Immunol. 1996 Oct 1;157(7):2939–2946. [PubMed] [Google Scholar]
  20. Tedder T. F., Zhou L. J., Engel P. The CD19/CD21 signal transduction complex of B lymphocytes. Immunol Today. 1994 Sep;15(9):437–442. doi: 10.1016/0167-5699(94)90274-7. [DOI] [PubMed] [Google Scholar]
  21. Todd S. C., Lipps S. G., Crisa L., Salomon D. R., Tsoukas C. D. CD81 expressed on human thymocytes mediates integrin activation and interleukin 2-dependent proliferation. J Exp Med. 1996 Nov 1;184(5):2055–2060. doi: 10.1084/jem.184.5.2055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wright M. D., Tomlinson M. G. The ins and outs of the transmembrane 4 superfamily. Immunol Today. 1994 Dec;15(12):588–594. doi: 10.1016/0167-5699(94)90222-4. [DOI] [PubMed] [Google Scholar]

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