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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Feb;87(4):1421–1425. doi: 10.1073/pnas.87.4.1421

Cross-linking Fc receptors stimulate splenic non-B, non-T cells to secrete interleukin 4 and other lymphokines.

S Z Ben-Sasson 1, G Le Gros 1, D H Conrad 1, F D Finkelman 1, W E Paul 1
PMCID: PMC53487  PMID: 2106135

Abstract

Spleen cell populations depleted of both B and T lymphocytes produce interleukin 4 (IL-4) in response to stimulation with immunoglobulins bound to the surface of culture dishes. In the presence of interleukin 3 (IL-3), plate-bound (PB) IgE and PB-IgG1, IgG2a, and IgG2b are excellent stimulants, whereas PB-IgA and PB-IgM fail to stimulate IL-4 production. In the absence of IL-3, PB-IgE stimulates relatively modest production of IL-4, whereas PB-IgG2a generally does not. The response to PB-IgE is inhibited by soluble IgE; antibody to Fc gamma receptor II inhibits the response to PB-IgG2a. Thus, separate receptors mediate these stimulations, and Fc receptor cross-linkage is required for IL-4 production. Depletion of cells expressing asialo-GM1 does not diminish IL-4 production in response to PB immunoglobulins, indicating that natural killer cells are not essential for non-B, non-T cell production of IL-4. In addition to IL-4, non-B, non-T cells produce IL-3, but no detectable interleukin 2 or interferon gamma. Non-B, non-T cells may be an important source of lymphokines in a variety of immune responses and may serve to amplify the effects of T cells of the TH2 type.

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Selected References

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  1. Brown M. A., Pierce J. H., Watson C. J., Falco J., Ihle J. N., Paul W. E. B cell stimulatory factor-1/interleukin-4 mRNA is expressed by normal and transformed mast cells. Cell. 1987 Aug 28;50(5):809–818. doi: 10.1016/0092-8674(87)90339-4. [DOI] [PubMed] [Google Scholar]
  2. Burd P. R., Rogers H. W., Gordon J. R., Martin C. A., Jayaraman S., Wilson S. D., Dvorak A. M., Galli S. J., Dorf M. E. Interleukin 3-dependent and -independent mast cells stimulated with IgE and antigen express multiple cytokines. J Exp Med. 1989 Jul 1;170(1):245–257. doi: 10.1084/jem.170.1.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Coffman R. L. Surface antigen expression and immunoglobulin gene rearrangement during mouse pre-B cell development. Immunol Rev. 1982;69:5–23. doi: 10.1111/j.1600-065x.1983.tb00446.x. [DOI] [PubMed] [Google Scholar]
  4. Crapper R. M., Schrader J. W. Frequency of mast cell precursors in normal tissues determined by an in vitro assay: antigen induces parallel increases in the frequency of P cell precursors and mast cells. J Immunol. 1983 Aug;131(2):923–928. [PubMed] [Google Scholar]
  5. Cuturi M. C., Anegón I., Sherman F., Loudon R., Clark S. C., Perussia B., Trinchieri G. Production of hematopoietic colony-stimulating factors by human natural killer cells. J Exp Med. 1989 Feb 1;169(2):569–583. doi: 10.1084/jem.169.2.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dexter T. M., Garland J., Scott D., Scolnick E., Metcalf D. Growth of factor-dependent hemopoietic precursor cell lines. J Exp Med. 1980 Oct 1;152(4):1036–1047. doi: 10.1084/jem.152.4.1036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  8. Finkelman F. D., Kessler S. W., Mushinski J. F., Potter M. IgD-secreting murine plasmacytomas: identification and partial characterization of two IgD myeloma proteins. J Immunol. 1981 Feb;126(2):680–687. [PubMed] [Google Scholar]
  9. Finkelman F. D., Snapper C. M., Mountz J. D., Katona I. M. Polyclonal activation of the murine immune system by a goat antibody to mouse IgD. IX. Induction of a polyclonal IgE response. J Immunol. 1987 May 1;138(9):2826–2830. [PubMed] [Google Scholar]
  10. Grabstein K., Eisenman J., Mochizuki D., Shanebeck K., Conlon P., Hopp T., March C., Gillis S. Purification to homogeneity of B cell stimulating factor. A molecule that stimulates proliferation of multiple lymphokine-dependent cell lines. J Exp Med. 1986 Jun 1;163(6):1405–1414. doi: 10.1084/jem.163.6.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Habu S., Fukui H., Shimamura K., Kasai M., Nagai Y., Okumura K., Tamaoki N. In vivo effects of anti-asialo GM1. I. Reduction of NK activity and enhancement of transplanted tumor growth in nude mice. J Immunol. 1981 Jul;127(1):34–38. [PubMed] [Google Scholar]
  12. Howard M., Farrar J., Hilfiker M., Johnson B., Takatsu K., Hamaoka T., Paul W. E. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982 Mar 1;155(3):914–923. doi: 10.1084/jem.155.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hu-Li J., Ohara J., Watson C., Tsang W., Paul W. E. Derivation of a T cell line that is highly responsive to IL-4 and IL-2 (CT.4R) and of an IL-2 hyporesponsive mutant of that line (CT.4S). J Immunol. 1989 Feb 1;142(3):800–807. [PubMed] [Google Scholar]
  14. Ishizaka K., Tomioka H., Ishizaka T. Mechanisms of passive sensitization. I. Presence of IgE and IgG molecules on human leukocytes. J Immunol. 1970 Dec;105(6):1459–1467. [PubMed] [Google Scholar]
  15. Jarrett E. E., Stewart D. C. Potentiation of rat reaginic (IgE) antibody by helminth infection. Simultaneous potentiation of separate reagins. Immunology. 1972 Nov;23(5):749–755. [PMC free article] [PubMed] [Google Scholar]
  16. Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kasahara T., Djeu J. Y., Dougherty S. F., Oppenheim J. J. Capacity of human large granular lymphocytes (LGL) to produce multiple lymphokines: interleukin 2, interferon, and colony stimulating factor. J Immunol. 1983 Nov;131(5):2379–2385. [PubMed] [Google Scholar]
  18. Kasai M., Iwamori M., Nagai Y., Okumura K., Tada T. A glycolipid on the surface of mouse natural killer cells. Eur J Immunol. 1980 Mar;10(3):175–180. doi: 10.1002/eji.1830100304. [DOI] [PubMed] [Google Scholar]
  19. Kupfer A., Swain S. L., Singer S. J. The specific direct interaction of helper T cells and antigen-presenting B cells. II. Reorientation of the microtubule organizing center and reorganization of the membrane-associated cytoskeleton inside the bound helper T cells. J Exp Med. 1987 Jun 1;165(6):1565–1580. doi: 10.1084/jem.165.6.1565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Le Gros G. S., Le Gros J. E., Watson J. D. The induction of lymphokine synthesis and cell growth in IL 3-dependent cell lines using antigen-antibody complexes. J Immunol. 1987 Jul 15;139(2):422–428. [PubMed] [Google Scholar]
  21. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  22. Leo O., Foo M., Sachs D. H., Samelson L. E., Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. doi: 10.1073/pnas.84.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Liu F. T., Bohn J. W., Ferry E. L., Yamamoto H., Molinaro C. A., Sherman L. A., Klinman N. R., Katz D. H. Monoclonal dinitrophenyl-specific murine IgE antibody: preparation, isolation, and characterization. J Immunol. 1980 Jun;124(6):2728–2737. [PubMed] [Google Scholar]
  24. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  25. Ohara J., Paul W. E. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. doi: 10.1038/315333a0. [DOI] [PubMed] [Google Scholar]
  26. Paul W. E. Pleiotropy and redundancy: T cell-derived lymphokines in the immune response. Cell. 1989 May 19;57(4):521–524. doi: 10.1016/0092-8674(89)90121-9. [DOI] [PubMed] [Google Scholar]
  27. Plaut M., Pierce J. H., Watson C. J., Hanley-Hyde J., Nordan R. P., Paul W. E. Mast cell lines produce lymphokines in response to cross-linkage of Fc epsilon RI or to calcium ionophores. Nature. 1989 May 4;339(6219):64–67. doi: 10.1038/339064a0. [DOI] [PubMed] [Google Scholar]
  28. Poo W. J., Conrad L., Janeway C. A., Jr Receptor-directed focusing of lymphokine release by helper T cells. Nature. 1988 Mar 24;332(6162):378–380. doi: 10.1038/332378a0. [DOI] [PubMed] [Google Scholar]
  29. Sarmiento M., Glasebrook A. L., Fitch F. W. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol. 1980 Dec;125(6):2665–2672. [PubMed] [Google Scholar]
  30. Tepper R. I., Pattengale P. K., Leder P. Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell. 1989 May 5;57(3):503–512. doi: 10.1016/0092-8674(89)90925-2. [DOI] [PubMed] [Google Scholar]
  31. Unkeless J. C., Scigliano E., Freedman V. H. Structure and function of human and murine receptors for IgG. Annu Rev Immunol. 1988;6:251–281. doi: 10.1146/annurev.iy.06.040188.001343. [DOI] [PubMed] [Google Scholar]
  32. Wodnar-Filipowicz A., Heusser C. H., Moroni C. Production of the haemopoietic growth factors GM-CSF and interleukin-3 by mast cells in response to IgE receptor-mediated activation. Nature. 1989 May 11;339(6220):150–152. doi: 10.1038/339150a0. [DOI] [PubMed] [Google Scholar]

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