Abstract
Dextran, of the variety commonly used as plasma expander, markedly altered antibody synthesis to an unrelated antigenic stimulus, SRBC, in two animal species, guinea pig and mouse. The time at which dextran was administered relative to antigen was found to be most critical for increasing or decreasing the number of IgM and IgG PFC. Furthermore, these times differed for the two species studied. Typically, when given to guinea pigs 6 h before SRBC, dextran caused a 20-fold rise in IgM-producing cells but had little effect upon IgG synthesis. However, if dextran preceded antigen by 24 h the same magnitude of increase was seen in IgG-forming cells while a decrease in IgM-producing cells occurred. In mice, a short 2 h interval between dextran and antigen favored cells synthesizing IgG and not those producing IgM. A longer 6 to 24 h lapse between dextran and antigen resulted again in an inverted pattern, i.e., an increase in IgM and a decrease in IgG-producing cells. In both species, if dextran was given 48 h before antigen, synthesis of IgG markedly decreased. At the cellular level dextran activated those B cells already in the vascular compartment. In stimulating the IgM response to SRBC, dextran appears either to substitute for T cells or to amplify the effects of that small number of T cells still present in bone marrow preparations. Dextran-altered mouse B cells synthesized SRBC-specific IgG in the presence of normal T cells at an earlier time than did normal B and T cells. However, dextran was unable to cause blastogenesis in vitro of guinea pig lymph node cells or mouse B, T, and spleen cells. The data suggest at least two effects that T cells exert upon B cells. One is to stimulate more B cells to produce IgM, a function accomplished by endotoxins, PWM, PPD, and the simple polysaccharide dextran. The other is to trigger shifts in synthesis of immunoglobulins M and G. Our observations are compatible with the view that a single cell is capable of synthesizing both of these immunoglobulins and that the stimulating factor for one may cause cessation of the other.
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- Allison A. C., Davies A. J. Requirement of thymus-dependent lymphocytes for potentiation by adjuvants of antibody formation. Nature. 1971 Oct 1;233(5318):330–332. doi: 10.1038/233330a0. [DOI] [PubMed] [Google Scholar]
- Andersson B., Blomgren H. Evidence for thymus-independent humoral antibody production in mice against polyvinylpyrrolidone and E. coli lipopolysaccharide. Cell Immunol. 1971 Oct;2(5):411–424. doi: 10.1016/0008-8749(71)90052-9. [DOI] [PubMed] [Google Scholar]
- Andersson J., Möller G., Sjöberg O. Selective induction of DNA synthesis in T and B lymphocytes. Cell Immunol. 1972 Aug;4(4):381–393. doi: 10.1016/0008-8749(72)90040-8. [DOI] [PubMed] [Google Scholar]
- Andersson J., Sjöberg O., Möller G. Induction of immunoglobulin and antibody synthesis in vitro by lipopolysaccharides. Eur J Immunol. 1972 Aug;2(4):349–353. doi: 10.1002/eji.1830020410. [DOI] [PubMed] [Google Scholar]
- Andersson J., Sjöberg O., Möller G. Mitogens as probes for immunocyte activation and cellular cooperation. Transplant Rev. 1972;11:131–177. doi: 10.1111/j.1600-065x.1972.tb00048.x. [DOI] [PubMed] [Google Scholar]
- Blomgren H., Svedmyr E. Evidence for thymic dependence of PHA-reactive cells in spleen and lymph nodes and independence in bone marrow. J Immunol. 1971 Mar;106(3):835–841. [PubMed] [Google Scholar]
- Byfield P. Increased plaque-forming cell response to pneumococcal polysaccharide type 3-coated sheep erythrocytes after priming with erythrocytes but not with polysaccharide. Cell Immunol. 1972 Apr;3(4):616–622. doi: 10.1016/0008-8749(72)90123-2. [DOI] [PubMed] [Google Scholar]
- Del Guercio P., Leuchars E. The immune response in mice to the haptenic determinant DNP coupled to a thymus-independent carrier (levan). J Immunol. 1972 Nov;109(5):951–956. [PubMed] [Google Scholar]
- Diamantstein T., Wagner B., Odenwald M. V., Schulz G. Stimulation of humoral antibody formation by polyanions. IV. The effects of dextran sulfate on the kinetics of secondary immune response in mice. Eur J Immunol. 1971 Dec;1(6):426–429. doi: 10.1002/eji.1830010604. [DOI] [PubMed] [Google Scholar]
- Dresser D. W. The role of T cells and adjuvant in the immune response of mice to foreign erythrocytes. Eur J Immunol. 1972 Feb;2(1):50–57. doi: 10.1002/eji.1830020111. [DOI] [PubMed] [Google Scholar]
- Dresser D. W., Wortis D. H. Use of an antiglobulin serum to detect cells producing antibody with low haemolytic efficiency. Nature. 1965 Nov 27;208(5013):859–861. doi: 10.1038/208859a0. [DOI] [PubMed] [Google Scholar]
- Dutton R. W. Inhibitory and stimulatory effects of concanavalin A on the response of mouse spleen cell suspensions to antigen. I. Characterization of the inhibitory cell activity. J Exp Med. 1972 Dec 1;136(6):1445–1460. doi: 10.1084/jem.136.6.1445. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finger H., Emmerling P., Büsse M. Increased priming for the secondary response in mice to sheep erythrocytes by bacterial endotoxins. Int Arch Allergy Appl Immunol. 1970;38(6):598–606. doi: 10.1159/000230315. [DOI] [PubMed] [Google Scholar]
- HUMPHREY J. H., PARROTT D. M., EAST J. STUDIES ON GLOBULIN AND ANTIBODY PRODUCTION IN MICE THYMECTOMIZED AT BIRTH. Immunology. 1964 Jul;7:419–439. [PMC free article] [PubMed] [Google Scholar]
- Howard J. G., Christie G. H., Courtenay B. M., Leuchars E., Davies A. J. Studies on immunological paralysis. VI. Thymic-independence of tolerance and immunity to type 3 pneumococcal polysaccharide. Cell Immunol. 1971 Dec;2(6):614–626. doi: 10.1016/0008-8749(71)90009-8. [DOI] [PubMed] [Google Scholar]
- Howe M. L., Battisto J. R. In vitro detection of spontaneously occurring delayed-type iso-hypersensitivity. Immunology. 1971 Mar;20(3):407–413. [PMC free article] [PubMed] [Google Scholar]
- Hunter P., Munro A. J. Response of mice to rabbit Fab' 2 and Fab'. Thymus independence of IgM response and thymus dependence of IgG response. Immunology. 1972 Jul;23(1):69–80. [PMC free article] [PubMed] [Google Scholar]
- Ito T., Shearer G. M., Trizio D., Cudkowicz G. B cell activation in vivo by nonantigen-specific interaction with T cells. Frequency of immune responses increased by immunization with two antigens. J Exp Med. 1972 Aug 1;136(2):381–386. doi: 10.1084/jem.136.2.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Janossy G., Greaves M. F. Lymphocyte activation. I. Response of T and B lymphocytes to phytomitogens. Clin Exp Immunol. 1971 Oct;9(4):483–498. [PMC free article] [PubMed] [Google Scholar]
- Janossy G., Greaves M. F. Lymphocyte activation. II. discriminating stimulation of lymphocyte subpopulations by phytomitogens and heterologous antilymphocyte sera. Clin Exp Immunol. 1972 Mar;10(3):525–536. [PMC free article] [PubMed] [Google Scholar]
- Jerne N. K., Nordin A. A. Plaque Formation in Agar by Single Antibody-Producing Cells. Science. 1963 Apr 26;140(3565):405–405. doi: 10.1126/science.140.3565.405. [DOI] [PubMed] [Google Scholar]
- Jones J. M., Kind P. D. Enhancing effect of bacterial endotoxins on bone marrow cells in the immune response to SRBC. J Immunol. 1972 May;108(5):1453–1455. [PubMed] [Google Scholar]
- KIND P., JOHNSON A. G. Studies on the adjuvant action of bacterial endotoxins on antibody formation. I. Time limitation of enhancing effect and restoration of antibody formation in x-irradiated rabbits. J Immunol. 1959 May;82(5):415–427. [PubMed] [Google Scholar]
- MERRITT K., JOHNSON A. G. STUDIES ON THE ADJUVANT ACTION OF BACTERIAL ENDOTOXINS ON ANTIBODY FORMATION. V. THE INFLUENCE OF ENDOTOXIN AND 5-FLUORO-2-DEOXYURIDINE ON THE PRIMARY ANTIBODY RESPONSE OF THE BALB MOUSE TO A PURIFIED PROTEIN ANTIGEN. J Immunol. 1963 Aug;91:266–272. [PubMed] [Google Scholar]
- Mond J. J., Takahashi T., Thorbecke G. J. Thymus-derived cell (T cell) activation by heterologous antigens as a replacement of specific immune T cells in the transfer of the secondary response to sheep erythrocytes. J Exp Med. 1972 Oct 1;136(4):715–721. doi: 10.1084/jem.136.4.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nilsson B. S., Sultzer B. M., Bullock W. W. Purified protein derivative of tuberculin induces immunoglobulin production in normal mouse spleen cells. J Exp Med. 1973 Jan 1;137(1):127–139. doi: 10.1084/jem.137.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ortiz-Ortiz L., Jaroslow B. N. Enhancement by the adjuvant, endotoxin, of an immune response induced in vitro. Immunology. 1970 Sep;19(3):387–399. [PMC free article] [PubMed] [Google Scholar]
- PEARMAIN G., LYCETTE R. R., FITZGERALD P. H. Tuberculin-induced mitosis in peripheral blood leucocytes. Lancet. 1963 Mar 23;1(7282):637–638. doi: 10.1016/s0140-6736(63)91275-3. [DOI] [PubMed] [Google Scholar]
- Parkhouse R. M., Janossy G., Greaves M. F. Selective stimulation of IgM synthesis in mouse B lymphocytes by pokeweed mitogen. Nat New Biol. 1972 Jan 5;235(53):21–23. doi: 10.1038/newbio235021a0. [DOI] [PubMed] [Google Scholar]
- SCHREK R. Cell transformations and mitoses produced in vitro by tuberculin purified protein derivative in human blood cells. Am Rev Respir Dis. 1963 May;87:734–738. doi: 10.1164/arrd.1963.87.5.734. [DOI] [PubMed] [Google Scholar]
- SHEE J. C. Myelosclerosis: an autoimmune disease. Lancet. 1963 Apr 6;1(7284):773–773. doi: 10.1016/s0140-6736(63)91599-x. [DOI] [PubMed] [Google Scholar]
- Schell K., Daniel K., Blazkovec A. A. Effects of anti-lymphocyte, anti-macrophage and anti-thymocyte serum IgG on the immune response. Int Arch Allergy Appl Immunol. 1971;41(2):286–301. doi: 10.1159/000230527. [DOI] [PubMed] [Google Scholar]
- Sjöberg O., Andersson J., Möller G. Lipopolysaccharide can substitute for helper cells in the antibody response in vitro. Eur J Immunol. 1972 Aug;2(4):326–331. doi: 10.1002/eji.1830020406. [DOI] [PubMed] [Google Scholar]
- Sterzl J., Ríha I. Detection of cells producing 7S antibodies by the plaque technique. Nature. 1965 Nov 27;208(5013):858–859. doi: 10.1038/208858a0. [DOI] [PubMed] [Google Scholar]
- Stobo J. D., Rosenthal A. S., Paul W. E. Functional heterogeneity of murine lymphoid cells. I. Responsiveness to and surface binding of concanavalin A and phytohemagglutinin. J Immunol. 1972 Jan;108(1):1–17. [PubMed] [Google Scholar]
- Sultzer B. M., Nilsson B. S. PPD tuberculin--a B-cell mitogen. Nat New Biol. 1972 Dec 13;240(102):198–200. doi: 10.1038/newbio240198a0. [DOI] [PubMed] [Google Scholar]
- Unanue E. R., Askonas B. A., Allison A. C. A role of macrophages in the stimulation of immune responses by adjuvants. J Immunol. 1969 Jul;103(1):71–78. [PubMed] [Google Scholar]