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. 1995 Sep;86(1):122–127.

Human lactoferrin induces phenotypic and functional changes in murine splenic B cells.

M Zimecki 1, J Mazurier 1, G Spik 1, J A Kapp 1
PMCID: PMC1383819  PMID: 7590872

Abstract

The immunotropic activities of human lactoferrin were studied with respect to phenotypic and functional changes in murine splenic B cells. Phenotypic changes were induced by human lactoferrin in splenic B-cell fractions separated by buoyant density. B cells from 7-8-day-old BALB/c mice isolated from a 50/60% Percoll gradient, gained characteristic features of more mature B cells manifested by an increase of surface IgD and complement receptor expression. Incubation of the analogous B-cell fraction from adult mice with human lactoferrin resulted in minor changes in relation to IgM and IgD expression. Besides induction of phenotypic changes on immature B cells, human lactoferrin enabled B cells from normal newborn and adult immunodeficient CBA/N mice to present antigen to an antigen-specific T-helper type 2 (Th2) cell line. We conclude that human lactoferrin acts as a maturation factor for B cells with regard to their phenotype and function.

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Selected References

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  1. Brines R. D., Klaus G. G. Inhibition of lipopolysaccharide-induced activation of immature B cells by anti-mu and anti-delta antibodies and its modulation by interleukin-4. Int Immunol. 1992 Jul;4(7):765–771. doi: 10.1093/intimm/4.7.765. [DOI] [PubMed] [Google Scholar]
  2. Crouch S. P., Slater K. J., Fletcher J. Regulation of cytokine release from mononuclear cells by the iron-binding protein lactoferrin. Blood. 1992 Jul 1;80(1):235–240. [PubMed] [Google Scholar]
  3. Gelfand M. C., Elfenbein G. J., Frank M. M., Paul W. E. Ontogeny of B lymphocytes. II. Relative rates of appearance of lymphocytes bearing surface immunoglobulin and complement receptors. J Exp Med. 1974 May 1;139(5):1125–1141. doi: 10.1084/jem.139.5.1125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hashizume S., Kuroda K., Murakami H. Identification of lactoferrin as an essential growth factor for human lymphocytic cell lines in serum-free medium. Biochim Biophys Acta. 1983 Dec 19;763(4):377–382. doi: 10.1016/0167-4889(83)90099-x. [DOI] [PubMed] [Google Scholar]
  5. Kearney J. F., Cooper M. D., Klein J., Abney E. R., Parkhouse R. M., Lawton A. R. Ontogeny of Ia and IgD on IgM-bearing B lymphocytes in mice. J Exp Med. 1977 Jul 1;146(1):297–301. doi: 10.1084/jem.146.1.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kimoto M., Fathman C. G. Antigen-reactive T cell clones. I. Transcomplementing hybrid I-A-region gene products function effectively in antigen presentation. J Exp Med. 1980 Oct 1;152(4):759–770. doi: 10.1084/jem.152.4.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lay W. H., Nussenzweig V. Receptors for complement of leukocytes. J Exp Med. 1968 Nov 1;128(5):991–1009. doi: 10.1084/jem.128.5.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Leveugle B., Mazurier J., Legrand D., Mazurier C., Montreuil J., Spik G. Lactotransferrin binding to its platelet receptor inhibits platelet aggregation. Eur J Biochem. 1993 May 1;213(3):1205–1211. doi: 10.1111/j.1432-1033.1993.tb17871.x. [DOI] [PubMed] [Google Scholar]
  9. MONTREUIL J., TONNELAT J., MULLET S. [Preparation and properties of lactosiderophilin (lactotransferrin) of human milk]. Biochim Biophys Acta. 1960 Dec 18;45:413–421. doi: 10.1016/0006-3002(60)91478-5. [DOI] [PubMed] [Google Scholar]
  10. Machnicki M., Zimecki M., Zagulski T. Lactoferrin regulates the release of tumour necrosis factor alpha and interleukin 6 in vivo. Int J Exp Pathol. 1993 Oct;74(5):433–439. [PMC free article] [PubMed] [Google Scholar]
  11. Masson P. L., Heremans J. F., Schonne E. Lactoferrin, an iron-binding protein in neutrophilic leukocytes. J Exp Med. 1969 Sep 1;130(3):643–658. doi: 10.1084/jem.130.3.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mazurier J., Legrand D., Hu W. L., Montreuil J., Spik G. Expression of human lactotransferrin receptors in phytohemagglutinin-stimulated human peripheral blood lymphocytes. Isolation of the receptors by antiligand-affinity chromatography. Eur J Biochem. 1989 Feb 1;179(2):481–487. doi: 10.1111/j.1432-1033.1989.tb14578.x. [DOI] [PubMed] [Google Scholar]
  13. Mazurier J., Spik G. Comparative study of the iron-binding properties of human transferrins. I. Complete and sequential iron saturation and desaturation of the lactotransferrin. Biochim Biophys Acta. 1980 May 7;629(2):399–408. doi: 10.1016/0304-4165(80)90112-9. [DOI] [PubMed] [Google Scholar]
  14. Miyazawa K., Mantel C., Lu L., Morrison D. C., Broxmeyer H. E. Lactoferrin-lipopolysaccharide interactions. Effect on lactoferrin binding to monocyte/macrophage-differentiated HL-60 cells. J Immunol. 1991 Jan 15;146(2):723–729. [PubMed] [Google Scholar]
  15. Morris J. F., Hoyer J. T., Pierce S. K. Antigen presentation for T cell interleukin-2 secretion is a late acquisition of neonatal B cells. Eur J Immunol. 1992 Nov;22(11):2923–2928. doi: 10.1002/eji.1830221125. [DOI] [PubMed] [Google Scholar]
  16. Narendran A., Ramsden D., Cumano A., Tanaka T., Wu G. E., Paige C. J. B cell developmental defects in X-linked immunodeficiency. Int Immunol. 1993 Feb;5(2):139–144. doi: 10.1093/intimm/5.2.139. [DOI] [PubMed] [Google Scholar]
  17. Rochard E., Legrand D., Lecocq M., Hamelin R., Crepin M., Montreuil J., Spik G. Characterization of lactotransferrin receptor in epithelial cell lines from non-malignant human breast, benign mastopathies and breast carcinomas. Anticancer Res. 1992 Nov-Dec;12(6B):2047–2051. [PubMed] [Google Scholar]
  18. Roehm N. W., Rodgers G. H., Hatfield S. M., Glasebrook A. L. An improved colorimetric assay for cell proliferation and viability utilizing the tetrazolium salt XTT. J Immunol Methods. 1991 Sep 13;142(2):257–265. doi: 10.1016/0022-1759(91)90114-u. [DOI] [PubMed] [Google Scholar]
  19. Scher I., Berning A. K., Kessler S., Finkelman F. D. Development of B lymphocytes in the mouse; studies of the frequency and distribution of surface IgM and IgD in normal and immune-defective CBA/N F1 mice. J Immunol. 1980 Oct;125(4):1686–1693. [PubMed] [Google Scholar]
  20. Scher I. The CBA/N mouse strain: an experimental model illustrating the influence of the X-chromosome on immunity. Adv Immunol. 1982;33:1–71. doi: 10.1016/s0065-2776(08)60834-2. [DOI] [PubMed] [Google Scholar]
  21. Schittek B., Rajewsky K. Natural occurrence and origin of somatically mutated memory B cells in mice. J Exp Med. 1992 Aug 1;176(2):427–438. doi: 10.1084/jem.176.2.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schryvers A. B., Morris L. J. Identification and characterization of the human lactoferrin-binding protein from Neisseria meningitidis. Infect Immun. 1988 May;56(5):1144–1149. doi: 10.1128/iai.56.5.1144-1149.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Smith H. R., Yaffe L. J., Chused T. M., Raveche E. S., Klinman D. M., Steinberg A. D. Analysis of B-cell subpopulations. I. Relationships among splenic xid, Ly 1+, and Lyb 5+ B cells. Cell Immunol. 1985 Apr 15;92(1):190–196. doi: 10.1016/0008-8749(85)90077-2. [DOI] [PubMed] [Google Scholar]
  24. Spik G., Strecker G., Fournet B., Bouquelet S., Montreuil J., Dorland L., van Halbeek H., Vliegenthart J. F. Primary structure of the glycans from human lactotransferrin. Eur J Biochem. 1982 Jan;121(2):413–419. doi: 10.1111/j.1432-1033.1982.tb05803.x. [DOI] [PubMed] [Google Scholar]
  25. Vitetta E. S., Melcher U., McWilliams M., Lamm M. E., Phillips-Quagliata J. M., Uhr J. W. Cell surface immunoglobulin. XI. The appearance of an IgD-like molecule on murine lymphoid cells during ontogeny. J Exp Med. 1975 Jan 1;141(1):206–215. doi: 10.1084/jem.141.1.206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zagulski T., Lipiński P., Zagulska A., Broniek S., Jarzabek Z. Lactoferrin can protect mice against a lethal dose of Escherichia coli in experimental infection in vivo. Br J Exp Pathol. 1989 Dec;70(6):697–704. [PMC free article] [PubMed] [Google Scholar]
  27. Zimecki M., Kapp J. A. Presentation of antigen by B cell subsets. III. Effects of interleukins on antigen presenting function and phenotype of immature B cells. Arch Immunol Ther Exp (Warsz) 1994;42(5-6):355–359. [PubMed] [Google Scholar]
  28. Zimecki M., Kapp J. A. Presentation of antigen by B cell subsets. IV. Defective T-B cell signalling causes inability to present antigen by B cells from immunodeficient mice. Arch Immunol Ther Exp (Warsz) 1994;42(5-6):361–367. [PubMed] [Google Scholar]
  29. Zimecki M., Mazurier J., Machnicki M., Wieczorek Z., Montreuil J., Spik G. Immunostimulatory activity of lactotransferrin and maturation of CD4- CD8- murine thymocytes. Immunol Lett. 1991 Sep;30(1):119–123. doi: 10.1016/0165-2478(91)90099-v. [DOI] [PubMed] [Google Scholar]
  30. Zimecki M., Whiteley P. J., Pierce C. W., Kapp J. A. Presentation of antigen by B cells subsets. I. Lyb-5+ and Lyb-5- B cells differ in ability to stimulate antigen specific T cells. Arch Immunol Ther Exp (Warsz) 1994;42(2):115–123. [PubMed] [Google Scholar]

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