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. 1978 Jun 1;147(6):1755–1770. doi: 10.1084/jem.147.6.1755

Cellular and molecular requirements for X-linked, hapten-specific B- cell blockade in CBA/N mice

PMCID: PMC2184319  PMID: 308090

Abstract

CBA/N mice, a mutant CBA subline, harbor an X-linked B-cell defect which prevents them from mounting immune responses to certain thymic- independent antigens such as pneumococcal polysaccharides and haptenated-Ficoll derivatives. These mice and the hybrid male progeny of CBA/N females are also exquisitely sensitive to a hapten-specific blockade of their otherwise adequate immune responses to thymic- dependent antigens such as N-2,4-dinitrophenylated-hemocyanin (DNP- KLH). As little as 10 ng of a DNP-Ficoll conjugate given 2 h before immunization with a 5,000-fold greater dosage of DNP-KLH, virtually abolishes the 4th-day direct plaque-forming cell (PFC) response specific for DNP. Responding hybrid (CBA/N x C3H/HeN) female mice are resistant to such blockade even at DNP-Ficoll dosages increased by three orders of magnitude. The DNP hapten and Ficoll must be chemically joined for this blocking effect to occur, and increasing the hapten derivatization of Ficoll increases its blockade-invoking capacity. Significant blockade can be produced by administering DNP-Ficoll as early as 4 days before or as late as 4 h after immunization with DNP- KLH. All currently available data point to the defective B cell as the target of this hapten-polysaccharide-mediated blockade. Mice bearing B memory cells, however, are refractory to such blockade. In addition, DNP-Ficoll injections which cause virtually total blockade of 4th-day primary direct PFC responses to DNP-KLH have little or no effect on the development of DNP-reactive B-cell memory measured at either 8 or 30 days. These findings suggest very different blockade susceptibilities for B cells or their precursors at various stages of differentiative development. Our findings also lead to the formulation of testable hypotheses regarding the mechanism of this selective B-cell blockade phenomenon.

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Selected References

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  1. Ahmed A., Scher I., Sharrow S. O., Smith A. H., Paul W. E., Sachs D. H., Sell K. W. B-lymphocyte heterogeneity: development and characterization of an alloantiserum which distinguishes B-lymphocyte differentiation alloantigens. J Exp Med. 1977 Jan 1;145(1):101–110. doi: 10.1084/jem.145.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Amsbaugh D. F., Hansen C. T., Prescott B., Stashak P. W., Barthold D. R., Baker P. J. Genetic control of the antibody response to type 3 pneumococcal polysaccharide in mice. I. Evidence that an X-linked gene plays a decisive role in determining responsiveness. J Exp Med. 1972 Oct 1;136(4):931–949. doi: 10.1084/jem.136.4.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baker P. J., Stashak P. W., Amsbaugh D. F., Prescott B. Characterization of the antibody response to type 3 pneumococcal polysaccharide at the cellular level. II. Studies on the relative rate of antibody synthesis and release by antibody-producing cells. Immunology. 1971 Apr;20(4):481–492. [PMC free article] [PubMed] [Google Scholar]
  4. Desaymard C., Pearce B., Feldmann M. Role of epitope density in the induction of tolerance and immunity with thymus-independent antigens. III. Interaction of epitope density and receptor avidity. Eur J Immunol. 1976 Sep;6(9):646–650. doi: 10.1002/eji.1830060910. [DOI] [PubMed] [Google Scholar]
  5. Desaymard C., Waldmann H. Evidence for the inactivation of precursor B cells in high dose unresponsiveness. Nature. 1976 Dec 23;264(5588):780–782. doi: 10.1038/264780a0. [DOI] [PubMed] [Google Scholar]
  6. Dintzis H. M., Dintzis R. Z., Vogelstein B. Molecular determinants of immunogenicity: the immunon model of immune response. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3671–3675. doi: 10.1073/pnas.73.10.3671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Finkelman F. D., Smith A. H., Scher I., Paul W. E. Abnormal ratio of membrane immunoglobulin classes in mice with an X-linked B-lymphocyte defect. J Exp Med. 1975 Nov 1;142(5):1316–1321. doi: 10.1084/jem.142.5.1316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Inman J. K., Merchant B., Claflin L., Tacey S. E. Coupling of large haptens to proteins and cell surfaces: preparation of stable, optimally sensitized erythrocytes for hapten-specific, hemolytic plaque assays. Immunochemistry. 1973 Mar;10(3):165–174. doi: 10.1016/0019-2791(73)90005-0. [DOI] [PubMed] [Google Scholar]
  9. Inman J. K., Merchant B., Tacey S. E. Synthesis of large haptenic compounds having a common functional group that permits covalent linkage to proteins, cell surfaces, and adsorbents. Immunochemistry. 1973 Mar;10(3):153–163. doi: 10.1016/0019-2791(73)90004-9. [DOI] [PubMed] [Google Scholar]
  10. Inman J. K. Thymus-independent antigens: the preparation of covalent, hapten-ficoll conjugates. J Immunol. 1975 Feb;114(2 Pt 1):704–709. [PubMed] [Google Scholar]
  11. Klaus G. G. B cell tolerance induced by polymeric antigens. II. Effects of tolerance on hapten-binding lymphocyte levels in primary and secondary antibody responses. Eur J Immunol. 1976 Jun;5(6):366–372. doi: 10.1002/eji.1830050603. [DOI] [PubMed] [Google Scholar]
  12. Klaus G. G. B cell tolerance induced by polymeric antigens. IV. Antigen-mediated inhibition of antibody-forming cells. Eur J Immunol. 1976 Mar;6(3):200–207. doi: 10.1002/eji.1830060311. [DOI] [PubMed] [Google Scholar]
  13. Klaus G. G., Humphrey J. H. B cell tolerance induced by polymeric antigens. I. Comparison of the dose and epitope density requirements for inactivation of primed and unprimed B cells in vivo. Eur J Immunol. 1976 Jun;5(6):361–365. doi: 10.1002/eji.1830050602. [DOI] [PubMed] [Google Scholar]
  14. McMaster P. R., Owens J. D., Vannier W. E. The preparation and characterization of a thymic independent antigen: episilon-dinitrophenyl-L-lysine-Ficoll. Immunochemistry. 1977 Mar;14(3):189–196. doi: 10.1016/0019-2791(77)90193-8. [DOI] [PubMed] [Google Scholar]
  15. Merchant B., Petersen B. Comparative sensitivities of the hemolytic plaque-in-agar and microchamber assays for detection of rabbit immune cells. J Immunol. 1968 Nov;101(5):860–867. [PubMed] [Google Scholar]
  16. Merchant B., Snippe H., Lizzio E. F., Inman J. K. X-linked genetic control of hapten-polysaccharide-mediated specific immune unresponsiveness in CBA/N mice. J Immunol. 1978 Apr;120(4):1362–1368. [PubMed] [Google Scholar]
  17. Scher I., Ahmed A., Strong D. M., Steinberg A. D., Paul W. E. X-linked B-lymphocyte immune defect in CBA/HN mice. I. Studies of the function and composition of spleen cells. J Exp Med. 1975 Apr 1;141(4):788–803. [PMC free article] [PubMed] [Google Scholar]
  18. Scher I., Frantz M. M., Steinberg A. D. The genetics of the immune response to a synthetic double-stranded RNA in a mutant CBA mouse strain. J Immunol. 1973 May;110(5):1396–1401. [PubMed] [Google Scholar]
  19. Scher I., Sharrow S. O., Paul W. E. X-linked B-lymphocyte defect in CBA/N mice. III. Abnormal development of B-lymphocyte populations defined by their density of surface immunoglobulin. J Exp Med. 1976 Aug 1;144(2):507–518. doi: 10.1084/jem.144.2.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Scher I., Sharrow S. O., Wistar R., Jr, Asofsky R., Paul W. E. B-lymphocyte heterogeneity: ontogenetic development and organ distribution of B-lymphocyte populations defined by their density of surface immunoglobulin. J Exp Med. 1976 Aug 1;144(2):494–506. doi: 10.1084/jem.144.2.494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Scher I., Steinberg A. D., Berning A. K., Paul W. E. X-linked B-lymphocyte immune defect in CBA/N mice. II. Studies of the mechanisms underlying the immune defect. J Exp Med. 1975 Sep 1;142(3):637–650. doi: 10.1084/jem.142.3.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schrader J. W., Nossal G. J. Effector cell blockade. A new mechanism of immune hyporeactivity induced by multivalent antigens. J Exp Med. 1974 Jun 1;139(6):1582–1598. doi: 10.1084/jem.139.6.1582. [DOI] [PMC free article] [PubMed] [Google Scholar]

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