Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1991 Jan 1;173(1):265–268. doi: 10.1084/jem.173.1.265

Adoptive transfer of neonatal T lymphocytes rescues immunoglobulin production in mice with severe combined immune deficiency

PMCID: PMC2118747  PMID: 1985122

Abstract

Mice with the autosomal recessive severe combined immune deficiency (scid) mutation lack mature lymphocytes because of defective joining of T cell receptor and immunoglobulin (Ig) gene segments. Penetrance of this mutation is incomplete since 10-25% of SCID mice produce some T or B lymphocytes. This "leaky" phenotype could be due to a reversion of the mutation in some mice or to a constant, low frequency of functional lymphocytes generated in all SCID mice with variable survival of such cells. We report here that all SCID mice can be stimulated to produce functional B cells by the transfer of normal neonatal, but not adult, T cells. T cell-induced rescue of C.B-17scid B cells results in high levels of Ig expressing the Ighb allotype of the SCID recipient. These results show that all SCID mice generate some functional B cells, the majority of which do not survive in the absence of a subset of T cells present in high frequency in the neonate.

Full Text

The Full Text of this article is available as a PDF (420.2 KB).

Selected References

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

  1. Bosma G. C., Custer R. P., Bosma M. J. A severe combined immunodeficiency mutation in the mouse. Nature. 1983 Feb 10;301(5900):527–530. doi: 10.1038/301527a0. [DOI] [PubMed] [Google Scholar]
  2. Bosma G. C., Fried M., Custer R. P., Carroll A., Gibson D. M., Bosma M. J. Evidence of functional lymphocytes in some (leaky) scid mice. J Exp Med. 1988 Mar 1;167(3):1016–1033. doi: 10.1084/jem.167.3.1016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carroll A. M., Hardy R. R., Bosma M. J. Occurrence of mature B (IgM+, B220+) and T (CD3+) lymphocytes in scid mice. J Immunol. 1989 Aug 15;143(4):1087–1093. [PubMed] [Google Scholar]
  4. Ferrier P., Covey L. R., Li S. C., Suh H., Malynn B. A., Blackwell T. K., Morrow M. A., Alt F. W. Normal recombination substrate VH to DJH rearrangements in pre-B cell lines from scid mice. J Exp Med. 1990 Jun 1;171(6):1909–1918. doi: 10.1084/jem.171.6.1909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Habu S., Kimura M., Katsuki M., Hioki K., Nomura T. Correlation of T cell receptor gene rearrangements to T cell surface antigen expression and to serum immunoglobulin level in scid mice. Eur J Immunol. 1987 Oct;17(10):1467–1471. doi: 10.1002/eji.1830171013. [DOI] [PubMed] [Google Scholar]
  6. Havran W. L., Allison J. P. Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors. Nature. 1988 Sep 29;335(6189):443–445. doi: 10.1038/335443a0. [DOI] [PubMed] [Google Scholar]
  7. Lalor P. A., Herzenberg L. A., Adams S., Stall A. M. Feedback regulation of murine Ly-1 B cell development. Eur J Immunol. 1989 Mar;19(3):507–513. doi: 10.1002/eji.1830190315. [DOI] [PubMed] [Google Scholar]
  8. Miyama-Inaba M., Kuma S., Inaba K., Ogata H., Iwai H., Yasumizu R., Muramatsu S., Steinman R. M., Ikehara S. Unusual phenotype of B cells in the thymus of normal mice. J Exp Med. 1988 Aug 1;168(2):811–816. doi: 10.1084/jem.168.2.811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Petrini J. H., Carroll A. M., Bosma M. J. T-cell receptor gene rearrangements in functional T-cell clones from severe combined immune deficient (scid) mice: reversion of the scid phenotype in individual lymphocyte progenitors. Proc Natl Acad Sci U S A. 1990 May;87(9):3450–3453. doi: 10.1073/pnas.87.9.3450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Riggs J. E., Stowers R. S., Mosier D. E. The immunoglobulin allotype contributed by peritoneal cavity B cells dominates in SCID mice reconstituted with allotype-disparate mixtures of splenic and peritoneal cavity B cells. J Exp Med. 1990 Aug 1;172(2):475–485. doi: 10.1084/jem.172.2.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Sakaguchi S., Sakaguchi N. Thymus and autoimmunity: capacity of the normal thymus to produce pathogenic self-reactive T cells and conditions required for their induction of autoimmune disease. J Exp Med. 1990 Aug 1;172(2):537–545. doi: 10.1084/jem.172.2.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Schuler W., Weiler I. J., Schuler A., Phillips R. A., Rosenberg N., Mak T. W., Kearney J. F., Perry R. P., Bosma M. J. Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell. 1986 Sep 26;46(7):963–972. doi: 10.1016/0092-8674(86)90695-1. [DOI] [PubMed] [Google Scholar]
  13. Shores E. W., Sharrow S. O., Uppenkamp I., Singer A. T cell receptor-negative thymocytes from SCID mice can be induced to enter the CD4/CD8 differentiation pathway. Eur J Immunol. 1990 Jan;20(1):69–77. doi: 10.1002/eji.1830200111. [DOI] [PubMed] [Google Scholar]
  14. Slack J., Der-Balian G. P., Nahm M., Davie J. M. Subclass restriction of murine antibodies. II. The IgG plaque-forming cell response to thymus-independent type 1 and type 2 antigens in normal mice and mice expressing an X-linked immunodeficiency. J Exp Med. 1980 Apr 1;151(4):853–862. doi: 10.1084/jem.151.4.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Smith H., Chen I. M., Kubo R., Tung K. S. Neonatal thymectomy results in a repertoire enriched in T cells deleted in adult thymus. Science. 1989 Aug 18;245(4919):749–752. doi: 10.1126/science.2788921. [DOI] [PubMed] [Google Scholar]
  16. Snapper C. M., Paul W. E. B cell stimulatory factor-1 (interleukin 4) prepares resting murine B cells to secrete IgG1 upon subsequent stimulation with bacterial lipopolysaccharide. J Immunol. 1987 Jul 1;139(1):10–17. [PubMed] [Google Scholar]
  17. Teale J. M. Abnormalities in isotype expression in CBA/N mice due to stimulatory environment rather than a B cell defect. J Immunol. 1983 Jan;130(1):72–77. [PubMed] [Google Scholar]
  18. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES