Abstract
Purified goat antibodies against mouse mu-chains and rabbit antibodies against mouse Ig determinants, and their Fab fragments, inhibited the development of IgM-bearing B cells in explant cultures of 14-day mouse fetal liver, and caused the disappearance of cell surface IgM in explant and dissociated cell cultures of more developed lymphoid tissues. While treatment of cultures of fetal or newborn liver, or adult bone marrow, with low concentrations (less than or equal to 10 mug/ml) of anti-Ig for less than or equal to 24 h caused the complete, but reversible, disappearance (modulation) of cell surface IgM, treatment for greater than or less than 48 h produced irreversible IgM suppression. In contrast, anti-Ig-induced suppression of cell surface IgM in cultures of adult spleen or lymph nodes required much higher concentrations of antibody (greater than or equal to 100 mug/ml) and was always reversible. These differences between immature and mature IgM-bearing cells could not be related to differences in the amount of surface IgM on the cells. The remarkable sensitivity of newly formed B cells to IgM modulation and irreversible IgM suppression when ligands bind to their Ig receptors, may have important implications for B-cell tolerance to self antigens.
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- Abney E. R., Parkhouse R. M. Candidate for immunoglobulin D present on murine B lymphocytes. Nature. 1974 Dec 13;252(5484):600–602. doi: 10.1038/252600a0. [DOI] [PubMed] [Google Scholar]
- Bonner W. A., Hulett H. R., Sweet R. G., Herzenberg L. A. Fluorescence activated cell sorting. Rev Sci Instrum. 1972 Mar;43(3):404–409. doi: 10.1063/1.1685647. [DOI] [PubMed] [Google Scholar]
- Chiller J. M., Habicht G. S., Weigle W. O. Kinetic differences in unresponsiveness of thymus and bone marrow cells. Science. 1971 Feb 26;171(3973):813–815. doi: 10.1126/science.171.3973.813. [DOI] [PubMed] [Google Scholar]
- Cosenza H., Köhler H. Specific suppression of the antibody response by antibodies to receptors. Proc Natl Acad Sci U S A. 1972 Sep;69(9):2701–2705. doi: 10.1073/pnas.69.9.2701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DRAY S. Effect of maternal isoantibodies on the quantitative expression of two allelic genes controlling gamma-globulin allotypic specificities. Nature. 1962 Aug 18;195:677–680. doi: 10.1038/195677a0. [DOI] [PubMed] [Google Scholar]
- Feldmann M., Pepys M. B. Role of C3 in in vitro lymphocyte cooperation. Nature. 1974 May 10;249(453):159–161. doi: 10.1038/249159a0. [DOI] [PubMed] [Google Scholar]
- Herzenberg L. A., Goodlin R. C., Rivera E. C. Immunoglobulin synthesis in mice: suppression by anti-allotype antibody. J Exp Med. 1967 Oct 1;126(4):701–713. doi: 10.1084/jem.126.4.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howard J. G., Mitchison N. A. Immunological tolerance. Prog Allergy. 1975;18:43–96. doi: 10.1159/000395256. [DOI] [PubMed] [Google Scholar]
- Kincade P. W., Lawton A. R., Bockman D. E., Cooper M. D. Suppression of immunoglobulin G synthesis as a result of antibody-mediated suppression of immunoglobulin M synthesis in chickens. Proc Natl Acad Sci U S A. 1970 Dec;67(4):1918–1925. doi: 10.1073/pnas.67.4.1918. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LEDERBERG J. Genes and antibodies. Science. 1959 Jun 19;129(3364):1649–1653. doi: 10.1126/science.129.3364.1649. [DOI] [PubMed] [Google Scholar]
- Lamm M. E., Boyse E. A., Old L. J., Lisowska-Bernstein B., Stockert E. Modulation of TL (thymus-leukemia) antigens by Fab-fragments of TL antibody. J Immunol. 1968 Jul;101(1):99–103. [PubMed] [Google Scholar]
- Lawton A. R., 3rd, Asofsky R., Hylton M. B., Cooper M. D. Suppression of immunoglobulin class synthesis in mice. I. Effects of treatment with antibody to -chain. J Exp Med. 1972 Feb 1;135(2):277–297. doi: 10.1084/jem.135.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Loor F., Forni L., Pernis B. The dynamic state of the lymphocyte membrane. Factors affecting the distribution and turnover of surface immunoglobulins. Eur J Immunol. 1972 Jun;2(3):203–212. doi: 10.1002/eji.1830020304. [DOI] [PubMed] [Google Scholar]
- Manning D. D., Jutila J. W. Immunosuppression of mice injected with heterologous anti-immunoglobulin heavy chain antisera. J Exp Med. 1972 Jun 1;135(6):1316–1333. doi: 10.1084/jem.135.6.1316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McKearn T. J., Stuart F. P., Fitch F. W. Anti-idiotypic antibody in rat transplantation immunity. I. Production of anti-idiotypic antibody in animals repeatedly immunized with alloantigens. J Immunol. 1974 Dec;113(6):1876–1882. [PubMed] [Google Scholar]
- Murgita R. A., Mattioli C. A., Tomasi T. B., Jr Production of a runting syndrome and selective A deficiency in mice by the administration of anti-heavy chain antisera. J Exp Med. 1973 Jul 1;138(1):209–228. doi: 10.1084/jem.138.1.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- NOSSAL G. J. The induction of immunological tolerance in rats to foreign erythrocytes. Aust J Exp Biol Med Sci. 1958 Jun;36(3):235–244. doi: 10.1038/icb.1958.25. [DOI] [PubMed] [Google Scholar]
- Nossal G. J., Pike B. L. Evidence for the clonal abortion theory of B-lymphocyte tolerance. J Exp Med. 1975 Apr 1;141(4):904–917. [PMC free article] [PubMed] [Google Scholar]
- Old L. J., Stockert E., Boyse E. A., Kim J. H. Antigenic modulation. Loss of TL antigen from cells exposed to TL antibody. Study of the phenomenon in vitro. J Exp Med. 1968 Mar 1;127(3):523–539. doi: 10.1084/jem.127.3.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Osmond D. G., Nossal G. J. Differentiation of lymphocytes in mouse bone marrow. II. Kinetics of maturation and renewal of antiglobulin-binding cells studied by double labeling. Cell Immunol. 1974 Jul;13(1):132–145. doi: 10.1016/0008-8749(74)90233-0. [DOI] [PubMed] [Google Scholar]
- Owen J. J., Cooper M. D., Raff M. C. In vitro generation of B lymphocytes in mouse foetal liver, a mammalian 'bursa equivalent'. Nature. 1974 May 24;249(455):361–363. doi: 10.1038/249361a0. [DOI] [PubMed] [Google Scholar]
- Raff M. C. Two distinct populations of peripheral lymphocytes in mice distinguishable by immunofluorescence. Immunology. 1970 Oct;19(4):637–650. [PMC free article] [PubMed] [Google Scholar]
- Reichlin M. Localizing antigenic determinants in human haemoglobin with mutants: molecular correlations of immunological tolerance. J Mol Biol. 1972 Mar 14;64(2):485–496. doi: 10.1016/0022-2836(72)90512-8. [DOI] [PubMed] [Google Scholar]
- Strayer D. S., Lee W. M., Rowley D. A., Köhler H. Anti-receptor antibody. II. Induction of long-term unresponsiveness in neonatal mice. J Immunol. 1975 Feb;114(2 Pt 2):728–733. [PubMed] [Google Scholar]
- Strober S. Maturation of B lymphocytes in the rat. II. Subpopulations of virgin B lymphocytes in the spleen and thoracic duct lymph. J Immunol. 1975 Feb;114(2 Pt 2):877–885. [PubMed] [Google Scholar]
- Unanue E. R., Perkins W. D., Karnovsky M. J. Endocytosis by lymphocytes of complexes of anti-Ig with membrane-bound Ig. J Immunol. 1972 Feb;108(2):569–572. [PubMed] [Google Scholar]
- Unanue E. R., Perkins W. D., Karnovsky M. J. Ligand-induced movement of lymphocyte membrane macromolecules. I. Analysis by immunofluorescence and ultrastructural radioautography. J Exp Med. 1972 Oct 1;136(4):885–906. doi: 10.1084/jem.136.4.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Weigle W. O. Recent observations and concepts in immunological unresponsiveness and autoimmunity. Clin Exp Immunol. 1971 Oct;9(4):437–447. [PMC free article] [PubMed] [Google Scholar]
- de Petris S., Raff M. C. Normal distribution, patching and capping of lymphocyte surface immunoglobulin studied by electron microscopy. Nat New Biol. 1973 Feb 28;241(113):257–259. doi: 10.1038/newbio241257a0. [DOI] [PubMed] [Google Scholar]