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The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1992 May 1;175(5):1169–1180. doi: 10.1084/jem.175.5.1169

B-less: a strain of profoundly B cell-deficient mice expressing a human lambda transgene

PMCID: PMC2119203  PMID: 1314882

Abstract

We have created several transgenic mouse strains that bear the human lambda light chain gene driven by its own promoter and a mouse immunoglobulin heavy chain enhancer. The transgene is expressed in many tissues, with particularly high levels of expression in the bone marrow, thymus, spleen, and lymph nodes. One of these transgenic lines, B-less, displays a dramatic phenotype characterized by an acute susceptibility to bacterial and viral infections. Analysis of this strain shows it to be profoundly deficient in both immature (pre-B) and mature B cells, as well as in circulating immunoglobulin. The pre-B and B cell defects are cell autonomous, as judged by cell culture and bone marrow graft chimeras. Despite this B cell deficiency, the T cell lineage appears grossly normal as assessed by flow cytometric analysis and by its response to mitogen stimulation. Since an independently derived transgenic strain bearing the same human lambda construct displays a partial B-less phenotype, it is likely that the B lineage deficiency is due to a dominant effect of transgene expression rather than to the insertional perturbation of an endogenous mouse gene. It is interesting that the deficiency phenotype is fully expressed in the FVB/N genetic background, but is suppressed in F1 hybrids formed between the FVB/N and C57BL/6 inbred strains. Evidently, there are one or more dominant genetic suppressors of B-less in the C57BL/6 genome.

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Selected References

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  1. Aihara Y., Bühring H. J., Aihara M., Klein J. An attempt to produce "pre-T" cell hybridomas and to identify their antigens. Eur J Immunol. 1986 Nov;16(11):1391–1399. doi: 10.1002/eji.1830161113. [DOI] [PubMed] [Google Scholar]
  2. Alt F. W., Yancopoulos G. D., Blackwell T. K., Wood C., Thomas E., Boss M., Coffman R., Rosenberg N., Tonegawa S., Baltimore D. Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J. 1984 Jun;3(6):1209–1219. doi: 10.1002/j.1460-2075.1984.tb01955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chesnut R. W., Grey H. M. Antigen presentation by B cells and its significance in T-B interactions. Adv Immunol. 1986;39:51–94. doi: 10.1016/s0065-2776(08)60348-x. [DOI] [PubMed] [Google Scholar]
  4. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Cooper M. D., Mulvaney D., Coutinho A., Cazenave P. A. A novel cell surface molecule on early B-lineage cells. Nature. 1986 Jun 5;321(6070):616–618. doi: 10.1038/321616a0. [DOI] [PubMed] [Google Scholar]
  7. Era T., Ogawa M., Nishikawa S., Okamoto M., Honjo T., Akagi K., Miyazaki J., Yamamura K. Differentiation of growth signal requirement of B lymphocyte precursor is directed by expression of immunoglobulin. EMBO J. 1991 Feb;10(2):337–342. doi: 10.1002/j.1460-2075.1991.tb07954.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grosschedl R., Weaver D., Baltimore D., Costantini F. Introduction of a mu immunoglobulin gene into the mouse germ line: specific expression in lymphoid cells and synthesis of functional antibody. Cell. 1984 Oct;38(3):647–658. doi: 10.1016/0092-8674(84)90259-9. [DOI] [PubMed] [Google Scholar]
  9. Hagman J., Lo D., Doglio L. T., Hackett J., Jr, Rudin C. M., Haasch D., Brinster R., Storb U. Inhibition of immunoglobulin gene rearrangement by the expression of a lambda 2 transgene. J Exp Med. 1989 Jun 1;169(6):1911–1929. doi: 10.1084/jem.169.6.1911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kincade P. W., Lee G., Watanabe T., Sun L., Scheid M. P. Antigens displayed on murine B lymphocyte precursors. J Immunol. 1981 Dec;127(6):2262–2268. [PubMed] [Google Scholar]
  11. Kitamura D., Roes J., Kühn R., Rajewsky K. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature. 1991 Apr 4;350(6317):423–426. doi: 10.1038/350423a0. [DOI] [PubMed] [Google Scholar]
  12. Korsmeyer S. J., Hieter P. A., Ravetch J. V., Poplack D. G., Waldmann T. A., Leder P. Developmental hierarchy of immunoglobulin gene rearrangements in human leukemic pre-B-cells. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7096–7100. doi: 10.1073/pnas.78.11.7096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kudo A., Melchers F. A second gene, VpreB in the lambda 5 locus of the mouse, which appears to be selectively expressed in pre-B lymphocytes. EMBO J. 1987 Aug;6(8):2267–2272. doi: 10.1002/j.1460-2075.1987.tb02500.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lamers M. C., Vakil M., Kearney J. F., Langhorne J., Paige C. J., Julius M. H., Mossmann H., Carsetti R., Köhler G. Immune status of a mu, kappa transgenic mouse line. Deficient response to bacterially related antigens. Eur J Immunol. 1989 Mar;19(3):459–468. doi: 10.1002/eji.1830190308. [DOI] [PubMed] [Google Scholar]
  15. Lane D. P., Lane E. B. A rapid antibody assay system for screening hybridoma cultures. J Immunol Methods. 1981;47(3):303–307. doi: 10.1016/0022-1759(81)90286-6. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. McKearn J. P., Rosenberg N. Mapping cell surface antigens on mouse pre-B cell lines. Eur J Immunol. 1985 Mar;15(3):295–298. doi: 10.1002/eji.1830150316. [DOI] [PubMed] [Google Scholar]
  18. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Muller W. J., Sinn E., Pattengale P. K., Wallace R., Leder P. Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell. 1988 Jul 1;54(1):105–115. doi: 10.1016/0092-8674(88)90184-5. [DOI] [PubMed] [Google Scholar]
  20. Nussenzweig M. C., Shaw A. C., Sinn E., Campos-Torres J., Leder P. Allelic exclusion in transgenic mice carrying mutant human IgM genes. J Exp Med. 1988 Jun 1;167(6):1969–1974. doi: 10.1084/jem.167.6.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nussenzweig M. C., Shaw A. C., Sinn E., Danner D. B., Holmes K. L., Morse H. C., 3rd, Leder P. Allelic exclusion in transgenic mice that express the membrane form of immunoglobulin mu. Science. 1987 May 15;236(4803):816–819. doi: 10.1126/science.3107126. [DOI] [PubMed] [Google Scholar]
  22. Pillai S., Baltimore D. Formation of disulphide-linked mu 2 omega 2 tetramers in pre-B cells by the 18K omega-immunoglobulin light chain. Nature. 1987 Sep 10;329(6135):172–174. doi: 10.1038/329172a0. [DOI] [PubMed] [Google Scholar]
  23. Rosenberg N., Baltimore D. A quantitative assay for transformation of bone marrow cells by Abelson murine leukemia virus. J Exp Med. 1976 Jun 1;143(6):1453–1463. doi: 10.1084/jem.143.6.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sakaguchi N., Melchers F. Lambda 5, a new light-chain-related locus selectively expressed in pre-B lymphocytes. Nature. 1986 Dec 11;324(6097):579–582. doi: 10.1038/324579a0. [DOI] [PubMed] [Google Scholar]
  25. Schmidt E. V., Pattengale P. K., Weir L., Leder P. Transgenic mice bearing the human c-myc gene activated by an immunoglobulin enhancer: a pre-B-cell lymphoma model. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6047–6051. doi: 10.1073/pnas.85.16.6047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Storb U., O'Brien R. L., McMullen M. D., Gollahon K. A., Brinster R. L. High expression of cloned immunoglobulin kappa gene in transgenic mice is restricted to B lymphocytes. Nature. 1984 Jul 19;310(5974):238–241. doi: 10.1038/310238a0. [DOI] [PubMed] [Google Scholar]
  27. Storb U. Transgenic mice with immunoglobulin genes. Annu Rev Immunol. 1987;5:151–174. doi: 10.1146/annurev.iy.05.040187.001055. [DOI] [PubMed] [Google Scholar]
  28. TILL J. E., McCULLOCH E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961 Feb;14:213–222. [PubMed] [Google Scholar]
  29. Vasicek T. J., Leder P. Structure and expression of the human immunoglobulin lambda genes. J Exp Med. 1990 Aug 1;172(2):609–620. doi: 10.1084/jem.172.2.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Whitlock C. A., Robertson D., Witte O. N. Murine B cell lymphopoiesis in long term culture. J Immunol Methods. 1984 Mar 16;67(2):353–369. doi: 10.1016/0022-1759(84)90475-7. [DOI] [PubMed] [Google Scholar]
  31. Yamada G., Ogawa M., Akagi K., Miyamoto H., Nakano N., Itoh S., Miyazaki J., Nishikawa S., Yamamura K., Taniguchi T. Specific depletion of the B-cell population induced by aberrant expression of human interferon regulatory factor 1 gene in transgenic mice. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):532–536. doi: 10.1073/pnas.88.2.532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yamamura K., Kudo A., Ebihara T., Kamino K., Araki K., Kumahara Y., Watanabe T. Cell-type-specific and regulated expression of a human gamma 1 heavy-chain immunoglobulin gene in transgenic mice. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2152–2156. doi: 10.1073/pnas.83.7.2152. [DOI] [PMC free article] [PubMed] [Google Scholar]

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