Skip to main content
NCBI home page
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
. 1993 Mar 1;90(5):1887–1891. doi: 10.1073/pnas.90.5.1887

Immunoglobulin D-deficient mice can mount normal immune responses to thymus-independent and -dependent antigens.

L Nitschke 1, M H Kosco 1, G Köhler 1, M C Lamers 1
PMCID: PMC45985  PMID: 8446604

Abstract

To examine the in vivo function of IgD we generated mice deficient for IgD by gene targeting. The IgD-mice show a reduced B-cell compartment with 30-50% less B cells in the spleen and lymph nodes but show a normal pre-B-cell compartment. The surface-IgD- B cells express two to three times more surface IgM than B cells of control animals. Serum concentrations of the immunoglobulin isotypes of IgD- mice are almost normal, indicating that surface-IgD expression is not necessary for class switching of B cells. Immunization experiments showed that IgD- mice could respond well to thymus-dependent and -independent antigens. After immunization normal germinal centers developed in the IgD- mice. These data suggest that IgD is not necessary for the induction of immune responses but may be important in homeostasis of cells in the B-cell compartment.

Full text

PDF
1887

Images in this article

1888Fig. 1
on p.1888
1890Fig. 5
on p.1890

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alés-Martínez J. E., Warner G. L., Scott D. W. Immunoglobulins D and M mediate signals that are qualitatively different in B cells with an immature phenotype. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6919–6923. doi: 10.1073/pnas.85.18.6919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bhattacharya A., Dorf M. E., Springer T. A. A shared alloantigenic determinant on Ia antigens encoded by the I-A and I-E subregions: evidence for I region gene duplication. J Immunol. 1981 Dec;127(6):2488–2495. [PubMed] [Google Scholar]
  3. Black S. J., van der Loo W., Loken M. R., Herzenberg L. A. Expression of IgD by murine lymphocytes. Loss of surface IgD indicates maturation of memory B cells. J Exp Med. 1978 Apr 1;147(4):984–996. doi: 10.1084/jem.147.4.984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cambier J. C., Vitetta E. S., Kettman J. R., Wetzel G. M., Uhr J. W. B-cell tolerance. III. Effect of papain-mediated cleavage of cell surface IgD on tolerance susceptibility of murine B cells. J Exp Med. 1977 Jul 1;146(1):107–117. doi: 10.1084/jem.146.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carsetti R., Köhler G., Lamers M. C. A role for immunoglobulin D: interference with tolerance induction. Eur J Immunol. 1993 Jan;23(1):168–178. doi: 10.1002/eji.1830230127. [DOI] [PubMed] [Google Scholar]
  6. Dennert G., Hyman R., Lesley J., Trowbridge I. S. Effects of cytotoxic monoclonal antibody specific for T200 glycoprotein on functional lymphoid cell populations. Cell Immunol. 1980 Aug 1;53(2):350–364. doi: 10.1016/0008-8749(80)90335-4. [DOI] [PubMed] [Google Scholar]
  7. Doetschman T. C., Eistetter H., Katz M., Schmidt W., Kemler R. The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J Embryol Exp Morphol. 1985 Jun;87:27–45. [PubMed] [Google Scholar]
  8. Finkelman F. D., Mond J. J., Metcalf E. S. Effects of neonatal anti-delta antibody treatment on the murine immune system. I. Suppression of development of surface IgD+ B cells and expansion of a surface IgM+ IgD- B lymphocyte population. J Immunol. 1983 Aug;131(2):593–600. [PubMed] [Google Scholar]
  9. Finkelman F. D., Scher I., Mond J. J., Kessler S., Kung J. T., Metcalf E. S. Polyclonal activation of the murine immune system by an antibody to IgD. II. Generation of polyclonal antibody production and cells with surface IgG. J Immunol. 1982 Aug;129(2):638–646. [PubMed] [Google Scholar]
  10. Froscher B. G., Klinman N. R. Strain-specific silencing of a predominant antidextran clonotype family. J Exp Med. 1985 Nov 1;162(5):1620–1633. doi: 10.1084/jem.162.5.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goodnow C. C., Crosbie J., Adelstein S., Lavoie T. B., Smith-Gill S. J., Brink R. A., Pritchard-Briscoe H., Wotherspoon J. S., Loblay R. H., Raphael K. Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature. 1988 Aug 25;334(6184):676–682. doi: 10.1038/334676a0. [DOI] [PubMed] [Google Scholar]
  12. Gray D., Chassoux D., MacLennan I. C., Bazin H. Selective depression of thymus-independent anti-DNP antibody responses induced by adult but not neonatal splenectomy. Clin Exp Immunol. 1985 Apr;60(1):78–86. [PMC free article] [PubMed] [Google Scholar]
  13. Hardy R. R., Hayakawa K., Haaijman J., Herzenberg L. A. B-cell subpopulations identifiable by two-color fluorescence analysis using a dual-laser FACS. Ann N Y Acad Sci. 1982;399:112–121. doi: 10.1111/j.1749-6632.1982.tb25667.x. [DOI] [PubMed] [Google Scholar]
  14. Herzenberg L. A., Black S. J., Tokuhisa T., Herzenberg L. A. Memory B cells at successive stages of differentiation. Affinity maturation and the role of IgD receptors. J Exp Med. 1980 May 1;151(5):1071–1087. doi: 10.1084/jem.151.5.1071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jacobson E. B., Baine Y., Chen Y. W., Flotte T., O'Neil M. J., Pernis B., Siskind G. W., Thorbecke G. J., Tonda P. Physiology of IgD. I. Compensatory phenomena in B lymphocyte activation in mice treated with anti-IgD antibodies. J Exp Med. 1981 Aug 1;154(2):318–332. doi: 10.1084/jem.154.2.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Layton J. E., Johnson G. R., Scott D. W., Nossal G. J. The anti-delta suppressed mouse. Eur J Immunol. 1978 May;8(5):325–330. doi: 10.1002/eji.1830080507. [DOI] [PubMed] [Google Scholar]
  17. Layton J. E., Teale J. M., Nossal G. J. Cloning of B cells positive or negative for surface IgD. II. Triggering and tolerance in the T-dependent splenic focus assay. J Immunol. 1979 Aug;123(2):709–713. [PubMed] [Google Scholar]
  18. Leptin M., Potash M. J., Grützmann R., Heusser C., Shulman M., Köhler G., Melchers F. Monoclonal antibodies specific for murine IgM I. Characterization of antigenic determinants on the four constant domains of the mu heavy chain. Eur J Immunol. 1984 Jun;14(6):534–542. doi: 10.1002/eji.1830140610. [DOI] [PubMed] [Google Scholar]
  19. Mansour S. L., Thomas K. R., Capecchi M. R. Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature. 1988 Nov 24;336(6197):348–352. doi: 10.1038/336348a0. [DOI] [PubMed] [Google Scholar]
  20. McFadden S. F., Vitetta E. S. sIgD-negative B cells from neonatal mice do not respond to the thymus-independent antigen TNP-BA in limiting dilution cultures. J Immunol. 1984 Apr;132(4):1717–1721. [PubMed] [Google Scholar]
  21. Oi V. T., Herzenberg L. A. Localization of murine Ig-1b and Ig-1a (IgG 2a) allotypic determinants detected with monoclonal antibodies. Mol Immunol. 1979 Dec;16(12):1005–1017. doi: 10.1016/0161-5890(79)90034-8. [DOI] [PubMed] [Google Scholar]
  22. Roes J., Rajewsky K. Cell autonomous expression of IgD is not essential for the maturation of conventional B cells. Int Immunol. 1991 Dec;3(12):1367–1371. doi: 10.1093/intimm/3.12.1367. [DOI] [PubMed] [Google Scholar]
  23. Schüppel R., Wilke J., Weiler E. Monoclonal anti-allotype antibody towards BALB/c IgM. Analysis of specificity and site of a V-C crossover in recombinant strain BALB-Igh-Va/Igh-Cb. Eur J Immunol. 1987 May;17(5):739–741. doi: 10.1002/eji.1830170527. [DOI] [PubMed] [Google Scholar]
  24. Springer T., Galfrè G., Secher D. S., Milstein C. Monoclonal xenogeneic antibodies to murine cell surface antigens: identification of novel leukocyte differentiation antigens. Eur J Immunol. 1978 Aug;8(8):539–551. doi: 10.1002/eji.1830080802. [DOI] [PubMed] [Google Scholar]
  25. Stall A. M., Loken M. R. Allotypic specificities of murine IgD and IgM recognized by monoclonal antibodies. J Immunol. 1984 Feb;132(2):787–795. [PubMed] [Google Scholar]
  26. Thomas K. R., Capecchi M. R. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell. 1987 Nov 6;51(3):503–512. doi: 10.1016/0092-8674(87)90646-5. [DOI] [PubMed] [Google Scholar]
  27. Tisch R., Roifman C. M., Hozumi N. Functional differences between immunoglobulins M and D expressed on the surface of an immature B-cell line. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6914–6918. doi: 10.1073/pnas.85.18.6914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Vitetta E. S., Uhr J. W. IgD and B cell differentiation. Immunol Rev. 1977;37:50–88. doi: 10.1111/j.1600-065x.1977.tb00245.x. [DOI] [PubMed] [Google Scholar]
  29. Williams R. L., Hilton D. J., Pease S., Willson T. A., Stewart C. L., Gearing D. P., Wagner E. F., Metcalf D., Nicola N. A., Gough N. M. Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature. 1988 Dec 15;336(6200):684–687. doi: 10.1038/336684a0. [DOI] [PubMed] [Google Scholar]
  30. Yuan D., Witte P. L. Transcriptional regulation of mu and delta gene expression in bone marrow pre-B and B lymphocytes. J Immunol. 1988 Apr 15;140(8):2808–2814. [PubMed] [Google Scholar]
  31. Zan-Bar I., Barzilay M. The relationship between surface immunoglobulin isotype and immune function of murine B lymphocytes. V. IgD-bearing cells in immunological tolerance. Eur J Immunol. 1982 Oct;12(10):838–844. doi: 10.1002/eji.1830121008. [DOI] [PubMed] [Google Scholar]
  32. Zan-Bar I., Strober S., Vitetta E. S. The relationship between surface immunoglobulin isotype and immune function of murine B lymphocytes. IV. Role of IgD-bearing cells in the propagation of immunologic memory. J Immunol. 1979 Aug;123(2):925–930. [PubMed] [Google Scholar]
  33. Zitron I. M., Mosier D. E., Paul W. E. The role of surface IgD in the response to thymic-independent antigens. J Exp Med. 1977 Dec 1;146(6):1707–1718. doi: 10.1084/jem.146.6.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES