Int. Archs Allergy appl. Immun. 53: 50-55 (1977)
Relationships between ïgE Antibody Production and other Immune Responses I. Ontogénie Development of IgE Antibody-Producing Capacity in Mice
Yoshiro Imada, Kikuo Nomoto, Hiroyasu Yamada and Kenji Takeya Department of Microbiology, School of Medicine, Kyushu University, Fukuoka
Abstract. In adult C57BL/6 mice, a high-responder strain to ovalbumin, PCA and HA antibodies appeared at the same time after immunization. In young mice, on the other hand, the capacity to produce IgE antibodies against ovalbumin developed earlier than that to produce IgM or IgG antibodies.
Mutual relationships between IgM and IgG antibody production have been studied by many investigators in terms of kinetics of production after antigenic stimulation and phylogénie or ontogénie development. After antigenic stimulation of adult mammals, IgM antibodies are produced earlier than IgG antibodies. In phylogénie or ontogénie development, the capacity to produce IgM antibodies appears earlier than that to pro duce IgG antibodies, as reviewed by Good and Papermaster [1]. By contrast, only some information is available with respect to the relation of IgE production to other antibody responses. After antigenic stimula tion of adult animals, IgE antibodies were found to be raised in early stages together with IgM or IgG antibodies [2—6], Several investigators studied an increase in the ser Reccivcd: January 2, 1976.
um level of IgE in childhood as reviewed by Bennich and Johansson [7] . The serum lev el of IgE was found to increase slowly with increasing age. This information seems to be not sufficient to give definite understand ing as to the position and meaning of IgE antibody production in immune response as a whole. In the present paper, development of the capacity to produce IgE antibodies will be compared with that to produce IgM and IgG antibodies in C57BL/6 mice which have been reported to be high responders to ovalbumin (OA) [5, 6, 8, 9].
Materials and Methods Animals. Inbred mice of C57BL/6Ms and C3H/HeMs strains were obtained from the breed ing unit of Kyushu University, School of MediDownloaded by: University of Chicago Library 205.208.116.24 - 4/9/2018 4:01:47 PM
Introduction
Imada/Nomoto/Yamada/T akeya
Results
Strain Differences Adult C57BL/6, C3H/He and BCF, mice were immunized with OA in Al(OH)3 gel on days 0 and 30. Blood specimens were obtained on days 5, 10, 15, 30, and 37. The same experimental protocols were repeated three times and average values are present ed below. PCA antibodies became detecta ble on day 10 and reached peak values on day 15 in C57BL/6 mice of both sexes (fig. 1). PCA titers in the male group were slightly higher than those in the female group. By contrast, C3H/He mice did not produce detectable amounts of PCA anti bodies after the primary immunization. BCF, mice exhibited a pattern of PCA anti body production similar to that in C57BL/6, although titers in BCF, were lower than those in C57BL/6. After the secondary im munization on day 30, not only C57BL/6 and BCF, mice but also C3H/He mice pro duced large amounts of PCA antibodies. Total HA antibodies became detectable on day 10 in C57BL/6 and BCF, mice, but were not detectable in C3H/He after the pri mary immunization (fig. 2). In C57BL/6 and BCF, mice, 2-MER antibodies were produced on day 10 or 15. Large amounts of HA antibodies were produced in these three groups after the secondary immuniza tion and they consisted largely of 2-MER antibodies. Precise Time Course Study on Antibody Responses in Adult Mice The precise kinetics of IgE and IgM or IgG antibody production in the primary re sponse in adult C57BL/6 mice, were stud ied. Mice treated by the same protocol were divided into four groups. The first, second,
Downloaded by: University of Chicago Library 205.208.116.24 - 4/9/2018 4:01:47 PM
cine. Baby mice of C57BL/6Ms strain and F, hy brids between C57BL/6Ms and C3H/HeMs (BCF,) were raised in our laboratory. Ten-week-old mice were used as adult mice. Each experimental group consisted of eight animals. Inbred rats of SpragueDawley (SD) strain were obtained from the breed ing unit and female rats of 250-300 g body weight were used for passive cutaneous anaphylaxis (PCA) experiments. Immunization. Mice were injected with 0.5 ml i.p. of gel containing I /d of OA (Katayama Chemical, Osaka) and I ml of aluminum hydrox ide, Al(OH)3, as described by Levine and Vaz [10]. Blood specimens were obtained by retroorbital puncture from individual mice at various times af ter immunization. 0.1 ml of blood was obtained from each mouse and added to 0.15 ml of saline. The dilution of serum corresponded to 1:4. Titra tion of hemagglutinin (HA) was carried out on the diluted individual sera and assessment of PCA ti ters was carried out on the pooled, diluted sera of each group. Titration of IgE antibodies. Titers of IgE anti bodies were assessed by PCA in SD rats [11, 12]. 50/d of serial 4-fold dilutions of test samples were injected intracutaneously into the shaved backs of SD rats. 24 h later, 1.0 ml of 1°/« Evans blue solution containing 5 ml i.v. of OA was in jected. The rats were sacrificed and the reactions were read 20 min after the elicitation. A blue spot with an average diameter of 5 mm or more was regarded as a positive reaction. The test was set up in duplicate in different rats for each sample and the titer was expressed by mean of the reac tions of two animals. Variation of the titers be tween two animals was less than 4-fold. Titration of IgM and IgG antibodies. HA titers were assessed by passive hemagglutinin test. Sheep erythrocytes were sensitized with OA after treat ment with tannic acid according to the method of Weir [13]. The whole procedure of titration was carried out by conventional micromethods. Titra tion was done before and after the treatment of test sera with 0.1 M 2-mercaptoethanol (2-ME) at 37 C for 30 min. 2-ME-sensitivc and 2-ME-resistant antibodies were designated, respectively, as IgM and IgG for convenience. Total and 2-MEresistant (2-MER) titers arc presented in the re sults.
51
Imada/Nomoto/Yamada/Takeya
Fig. 1. Strain differences in PCA antibody re sponse to OA in 10-week-old mice. Mice were im munized with 1 /rg OA and 1 mg Al(OH>3 on days 0 and 30. 0 = PCA titers of females; • = PCA titers of males.
Fig. 2. Strain differences in HA antibody response to OA in 10-week-old mice. Mice were immunized with 1 n% OA and 1 mg Al(OH>3 on days 0 and 30. 0 = Total HA titers of females; • =total HA titers of males; A= 2-MER HA titers of females; A = 2-MER HA titers of males.
third and fourth groups were bled, respcctively, on days 4, 5, 6 and 7 after the immunization, and bleeding was repeated every 4 days in each group thereafter (fig. 3). PCA and total HA antibodies of high titers were
detected on day 7. The peak values of both antibodies were maintained beyond 22. 2-MER HA antibodies became detectable on day 8 and also maintained the peak value beyond day 22.
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52
Ontogénie Development of IgE in Mice
Log 2 HA
53
Log 2 H A
Fig. 4. Antibody responses to OA in 2-, 3-, and 4-week-old C57 BL/6 mice. Mice were immunized with 1 //g OA and 1 mg Al(OH)3. (o)= PCA titers; • = total HA titers; A = 2-MER HA titers.
tectable on day 16 and 2-MER HA anti bodies on day 22. When mice were immunized at 4 weeks of age, PCA and total HA antibodies ap peared on day 8 and reached peak values on day 9. These were maintained to day 22. 2-MER HA of low titers were detected from day 9 to day 22.
Discussion
C57BL/6 mice carrying H-21' histocom patibility antigens responded well to the im munization with OA as reported by several investigators [5, 8, 9], On the other hand,
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Ontogenic Development of the Capaci ties to Produce PCA and HA Antibodies C57BL/6 mice were immunized with OA in Al(OH)3 gel at 2, 3, and 4 weeks of age. Two or three groups were provided for each age-matched experiment. A group of mice were bled on day 4 and other groups on day 5 or 6. Bleeding was repeated every 4 days in each group thereafter. In the experiment with 2-week-old mice, PCA antibodies were detectable from day 9 to day 21, while total and 2-MER HA were negligible during the observation period. If a few sera contained very large amounts of PCA antibodies and others contained very small or none, the values of pooled sera might not reflect the real ones. PCA titers in individual mice were assessed on the 9th and 11th days in order to obtain the an swer to this question. The ratio of animals showing positive PCA was 7/8 on the 9th day and all mice exhibited positive reactions on the 11th day. In the experiment with 3-week-old mice, PCA antibodies were detectable on day 7 and reached the peak on day 9 followed by maintenance of the peak value to day 22. In this group, total HA antibodies became de-
Log 2 HA
Fig. 3. Antibody responses to OA in 10-week-old C57BL/6 mice. Mice were immunized with 1 //g OA and 1 mg AI(OH)3. o = PCA titers: «=10131 HA titers; A = 2-MER HA titers.
Imada/N omoto/Yamada/T akeya
54
References 1 Good, R. A. and Papermaster, B. W.: Ontogenic and phylogeny of adoptive immunity. Adv. Immunol. 4: 1-115 (1964). 2 Revoltella, R. and Ovary, Z.: Reagenic anti body production in different strain. Immunolo gy 17:45-54 (1971). 3 Lee, W. Y. and Sehon, A. H.: Suppression of reagenic antibody formation. I. Induction of hapten-specific tolerance. J. Immun. 114: 829-835 (1975). 4 Murphey, S. M.; Brown, S.; Miklos, N., and Fireman, P.: Rcagin synthesis in inbred strains of rats. Immunology 27: 245-253 (1974). 5 Vaz, N. M.; Phillips-Quagliata, J. M.; Levinne, B. B., and Vaz, E. M.: H-2-linked genetic con trol of immune responsiveness to ovalbumin and ovomucoid. J. exp. Med. 134: 1335-1348 (1971). 6 Vaz, F.. M.; Vaz, N. M„ and Levine, B. B.: Persistent formation of reagins in mice injected with low doses of ovalbumin. Immunology 21: 11-15(1971). 7 Bennich, H.; and Johansson, S. G. O.: Struc ture and function of human immunoglobulin E. Adv. Immunol. 13: 1-55 (1971). 8 Dunham, E. K.; Dorf. M. E.; Shrefflcr. D. C.. and Benacerraf, B.: Mapping the H-2-linked genes govering, respectively, the immune res ponses to a glutamic acid-alanine-tyrosine co polymer and to limiting doses of ovalbumin. J. Immun. Ill: 1621-1625 (1973). 9 Vaz, N. M.; Sovza, C. M. De, and Maia. L. C. S.: Genetic control of immune responsiveness in mice. Responsiveness to ovalbumin in (C57BLXDBA/2)F, mice. lnt. Archs Allergy appl. Immun. 46: 275-279 (1974). 10 Levine. B. B. and Vaz, N. M.: Effect of com binations of inbred strain, antigen, and antigen dose on immune responsiveness and reagin production in the mouse. A potential mouse model for immune aspects of human atopic al lergy. Int. Archs Allergy appl. Immun. 39: 156-171 (1970). 11 Mota, I. and Wong. D.: Homologous and het erologous passive cutaneous anaphylactic ac tivity of mouse antisera during the course of immunization. Life. Sci. 8: 813-820 (1969).
Downloaded by: University of Chicago Library 205.208.116.24 - 4/9/2018 4:01:47 PM
C3H/He mice carrying H-2k histocompati bility antigens responded poorly to the im munization with OA. High-responder C57BL/6 mice produced efficiently all of the IgM, IgG and IgE antibody classes, while low-responder C3H/He mice pro duced none of these classes of antibodies. C57BL/6xC3H/He F,-hybrid mice pro duced these antibodies as well as high-res ponder C57BL/6 mice. Therefore, the im mune response gene for OA may regulate the production of all classes of antibodies [5], In adult mice of JO weeks of age, IgE antibodies were produced at almost the same stages as IgM antibodies after immu nization with OA. When 2-week-old mice were immunized, only IgE antibodies were produced efficiently. When mice were im munized at 3 weeks of age, IgE antibodies were produced at an early stage, but IgM and IgG antibodies were only produced at a late stage. However, when mice were immu nized at 4 weeks of age, not only IgE but also IgM and IgG production took the pat terns similar to those in adult mice. There fore, in the process of ontogcnic develop ment, the capacity to produce IgE antibod ies appears to mature earlier than that to produce IgM and IgG antibodies. Wigzell and Stjernsward [14] reported that direct plaque-forming cells were detect able after immunization with sheep red blood cells in 7-day-old mice. Takeya and Nomoto [15] reported that 2-ME-sensitive antibodies were produced on day 10 after immunization with sheep red blood cells in 3-day-old mice. These results suggest that the capacity to produce IgM antibodies ap pears at a younger age than 2 or 3 weeks. This discrepancy may be due to differences in antigens.
12 König, W.; Okudaira, H„ and Ishizaka, K.: Specific binding of mouse IgE with rat mast cells. J. Immun. ! !2: 1652-1659 (1974). 13 Weir, D. M.: Handbook of experimental im munology (Blackwell, Oxford 1969). 14 Wigzell, H. and Stjernswärd, J.: Age-depen dent rise and fall of immunological reactivity in the CBA mice. J. natn. Cancer Inst. 37: 513-517 (1966).
55
15 Takeya, K. and Nomoto, K.: Characteristics of antibody response in young or thymectomized mice. J. Immun. 99: 831-836 (1967).
Correspondence to: Dr. Yoshiro Imada, Depart ment of Bacteriology, School of Medicine, Kyu shu University, 1-1, 3-Chome, Maidashi, Higashiku, Fukuoka City, 812 (Japan)
Downloaded by: University of Chicago Library 205.208.116.24 - 4/9/2018 4:01:47 PM
Ontogénie Development of IgE in Mice
Relationships between ïgE Antibody Production and other Immune Responses I. Ontogénie Development of IgE Antibody-Producing Capacity in Mice
Yoshiro Imada, Kikuo Nomoto, Hiroyasu Yamada and Kenji Takeya Department of Microbiology, School of Medicine, Kyushu University, Fukuoka
Abstract. In adult C57BL/6 mice, a high-responder strain to ovalbumin, PCA and HA antibodies appeared at the same time after immunization. In young mice, on the other hand, the capacity to produce IgE antibodies against ovalbumin developed earlier than that to produce IgM or IgG antibodies.
Mutual relationships between IgM and IgG antibody production have been studied by many investigators in terms of kinetics of production after antigenic stimulation and phylogénie or ontogénie development. After antigenic stimulation of adult mammals, IgM antibodies are produced earlier than IgG antibodies. In phylogénie or ontogénie development, the capacity to produce IgM antibodies appears earlier than that to pro duce IgG antibodies, as reviewed by Good and Papermaster [1]. By contrast, only some information is available with respect to the relation of IgE production to other antibody responses. After antigenic stimula tion of adult animals, IgE antibodies were found to be raised in early stages together with IgM or IgG antibodies [2—6], Several investigators studied an increase in the ser Reccivcd: January 2, 1976.
um level of IgE in childhood as reviewed by Bennich and Johansson [7] . The serum lev el of IgE was found to increase slowly with increasing age. This information seems to be not sufficient to give definite understand ing as to the position and meaning of IgE antibody production in immune response as a whole. In the present paper, development of the capacity to produce IgE antibodies will be compared with that to produce IgM and IgG antibodies in C57BL/6 mice which have been reported to be high responders to ovalbumin (OA) [5, 6, 8, 9].
Materials and Methods Animals. Inbred mice of C57BL/6Ms and C3H/HeMs strains were obtained from the breed ing unit of Kyushu University, School of MediDownloaded by: University of Chicago Library 205.208.116.24 - 4/9/2018 4:01:47 PM
Introduction
Imada/Nomoto/Yamada/T akeya
Results
Strain Differences Adult C57BL/6, C3H/He and BCF, mice were immunized with OA in Al(OH)3 gel on days 0 and 30. Blood specimens were obtained on days 5, 10, 15, 30, and 37. The same experimental protocols were repeated three times and average values are present ed below. PCA antibodies became detecta ble on day 10 and reached peak values on day 15 in C57BL/6 mice of both sexes (fig. 1). PCA titers in the male group were slightly higher than those in the female group. By contrast, C3H/He mice did not produce detectable amounts of PCA anti bodies after the primary immunization. BCF, mice exhibited a pattern of PCA anti body production similar to that in C57BL/6, although titers in BCF, were lower than those in C57BL/6. After the secondary im munization on day 30, not only C57BL/6 and BCF, mice but also C3H/He mice pro duced large amounts of PCA antibodies. Total HA antibodies became detectable on day 10 in C57BL/6 and BCF, mice, but were not detectable in C3H/He after the pri mary immunization (fig. 2). In C57BL/6 and BCF, mice, 2-MER antibodies were produced on day 10 or 15. Large amounts of HA antibodies were produced in these three groups after the secondary immuniza tion and they consisted largely of 2-MER antibodies. Precise Time Course Study on Antibody Responses in Adult Mice The precise kinetics of IgE and IgM or IgG antibody production in the primary re sponse in adult C57BL/6 mice, were stud ied. Mice treated by the same protocol were divided into four groups. The first, second,
Downloaded by: University of Chicago Library 205.208.116.24 - 4/9/2018 4:01:47 PM
cine. Baby mice of C57BL/6Ms strain and F, hy brids between C57BL/6Ms and C3H/HeMs (BCF,) were raised in our laboratory. Ten-week-old mice were used as adult mice. Each experimental group consisted of eight animals. Inbred rats of SpragueDawley (SD) strain were obtained from the breed ing unit and female rats of 250-300 g body weight were used for passive cutaneous anaphylaxis (PCA) experiments. Immunization. Mice were injected with 0.5 ml i.p. of gel containing I /d of OA (Katayama Chemical, Osaka) and I ml of aluminum hydrox ide, Al(OH)3, as described by Levine and Vaz [10]. Blood specimens were obtained by retroorbital puncture from individual mice at various times af ter immunization. 0.1 ml of blood was obtained from each mouse and added to 0.15 ml of saline. The dilution of serum corresponded to 1:4. Titra tion of hemagglutinin (HA) was carried out on the diluted individual sera and assessment of PCA ti ters was carried out on the pooled, diluted sera of each group. Titration of IgE antibodies. Titers of IgE anti bodies were assessed by PCA in SD rats [11, 12]. 50/d of serial 4-fold dilutions of test samples were injected intracutaneously into the shaved backs of SD rats. 24 h later, 1.0 ml of 1°/« Evans blue solution containing 5 ml i.v. of OA was in jected. The rats were sacrificed and the reactions were read 20 min after the elicitation. A blue spot with an average diameter of 5 mm or more was regarded as a positive reaction. The test was set up in duplicate in different rats for each sample and the titer was expressed by mean of the reac tions of two animals. Variation of the titers be tween two animals was less than 4-fold. Titration of IgM and IgG antibodies. HA titers were assessed by passive hemagglutinin test. Sheep erythrocytes were sensitized with OA after treat ment with tannic acid according to the method of Weir [13]. The whole procedure of titration was carried out by conventional micromethods. Titra tion was done before and after the treatment of test sera with 0.1 M 2-mercaptoethanol (2-ME) at 37 C for 30 min. 2-ME-sensitivc and 2-ME-resistant antibodies were designated, respectively, as IgM and IgG for convenience. Total and 2-MEresistant (2-MER) titers arc presented in the re sults.
51
Imada/Nomoto/Yamada/Takeya
Fig. 1. Strain differences in PCA antibody re sponse to OA in 10-week-old mice. Mice were im munized with 1 /rg OA and 1 mg Al(OH>3 on days 0 and 30. 0 = PCA titers of females; • = PCA titers of males.
Fig. 2. Strain differences in HA antibody response to OA in 10-week-old mice. Mice were immunized with 1 n% OA and 1 mg Al(OH>3 on days 0 and 30. 0 = Total HA titers of females; • =total HA titers of males; A= 2-MER HA titers of females; A = 2-MER HA titers of males.
third and fourth groups were bled, respcctively, on days 4, 5, 6 and 7 after the immunization, and bleeding was repeated every 4 days in each group thereafter (fig. 3). PCA and total HA antibodies of high titers were
detected on day 7. The peak values of both antibodies were maintained beyond 22. 2-MER HA antibodies became detectable on day 8 and also maintained the peak value beyond day 22.
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52
Ontogénie Development of IgE in Mice
Log 2 HA
53
Log 2 H A
Fig. 4. Antibody responses to OA in 2-, 3-, and 4-week-old C57 BL/6 mice. Mice were immunized with 1 //g OA and 1 mg Al(OH)3. (o)= PCA titers; • = total HA titers; A = 2-MER HA titers.
tectable on day 16 and 2-MER HA anti bodies on day 22. When mice were immunized at 4 weeks of age, PCA and total HA antibodies ap peared on day 8 and reached peak values on day 9. These were maintained to day 22. 2-MER HA of low titers were detected from day 9 to day 22.
Discussion
C57BL/6 mice carrying H-21' histocom patibility antigens responded well to the im munization with OA as reported by several investigators [5, 8, 9], On the other hand,
Downloaded by: University of Chicago Library 205.208.116.24 - 4/9/2018 4:01:47 PM
Ontogenic Development of the Capaci ties to Produce PCA and HA Antibodies C57BL/6 mice were immunized with OA in Al(OH)3 gel at 2, 3, and 4 weeks of age. Two or three groups were provided for each age-matched experiment. A group of mice were bled on day 4 and other groups on day 5 or 6. Bleeding was repeated every 4 days in each group thereafter. In the experiment with 2-week-old mice, PCA antibodies were detectable from day 9 to day 21, while total and 2-MER HA were negligible during the observation period. If a few sera contained very large amounts of PCA antibodies and others contained very small or none, the values of pooled sera might not reflect the real ones. PCA titers in individual mice were assessed on the 9th and 11th days in order to obtain the an swer to this question. The ratio of animals showing positive PCA was 7/8 on the 9th day and all mice exhibited positive reactions on the 11th day. In the experiment with 3-week-old mice, PCA antibodies were detectable on day 7 and reached the peak on day 9 followed by maintenance of the peak value to day 22. In this group, total HA antibodies became de-
Log 2 HA
Fig. 3. Antibody responses to OA in 10-week-old C57BL/6 mice. Mice were immunized with 1 //g OA and 1 mg AI(OH)3. o = PCA titers: «=10131 HA titers; A = 2-MER HA titers.
Imada/N omoto/Yamada/T akeya
54
References 1 Good, R. A. and Papermaster, B. W.: Ontogenic and phylogeny of adoptive immunity. Adv. Immunol. 4: 1-115 (1964). 2 Revoltella, R. and Ovary, Z.: Reagenic anti body production in different strain. Immunolo gy 17:45-54 (1971). 3 Lee, W. Y. and Sehon, A. H.: Suppression of reagenic antibody formation. I. Induction of hapten-specific tolerance. J. Immun. 114: 829-835 (1975). 4 Murphey, S. M.; Brown, S.; Miklos, N., and Fireman, P.: Rcagin synthesis in inbred strains of rats. Immunology 27: 245-253 (1974). 5 Vaz, N. M.; Phillips-Quagliata, J. M.; Levinne, B. B., and Vaz, E. M.: H-2-linked genetic con trol of immune responsiveness to ovalbumin and ovomucoid. J. exp. Med. 134: 1335-1348 (1971). 6 Vaz, F.. M.; Vaz, N. M„ and Levine, B. B.: Persistent formation of reagins in mice injected with low doses of ovalbumin. Immunology 21: 11-15(1971). 7 Bennich, H.; and Johansson, S. G. O.: Struc ture and function of human immunoglobulin E. Adv. Immunol. 13: 1-55 (1971). 8 Dunham, E. K.; Dorf. M. E.; Shrefflcr. D. C.. and Benacerraf, B.: Mapping the H-2-linked genes govering, respectively, the immune res ponses to a glutamic acid-alanine-tyrosine co polymer and to limiting doses of ovalbumin. J. Immun. Ill: 1621-1625 (1973). 9 Vaz, N. M.; Sovza, C. M. De, and Maia. L. C. S.: Genetic control of immune responsiveness in mice. Responsiveness to ovalbumin in (C57BLXDBA/2)F, mice. lnt. Archs Allergy appl. Immun. 46: 275-279 (1974). 10 Levine. B. B. and Vaz, N. M.: Effect of com binations of inbred strain, antigen, and antigen dose on immune responsiveness and reagin production in the mouse. A potential mouse model for immune aspects of human atopic al lergy. Int. Archs Allergy appl. Immun. 39: 156-171 (1970). 11 Mota, I. and Wong. D.: Homologous and het erologous passive cutaneous anaphylactic ac tivity of mouse antisera during the course of immunization. Life. Sci. 8: 813-820 (1969).
Downloaded by: University of Chicago Library 205.208.116.24 - 4/9/2018 4:01:47 PM
C3H/He mice carrying H-2k histocompati bility antigens responded poorly to the im munization with OA. High-responder C57BL/6 mice produced efficiently all of the IgM, IgG and IgE antibody classes, while low-responder C3H/He mice pro duced none of these classes of antibodies. C57BL/6xC3H/He F,-hybrid mice pro duced these antibodies as well as high-res ponder C57BL/6 mice. Therefore, the im mune response gene for OA may regulate the production of all classes of antibodies [5], In adult mice of JO weeks of age, IgE antibodies were produced at almost the same stages as IgM antibodies after immu nization with OA. When 2-week-old mice were immunized, only IgE antibodies were produced efficiently. When mice were im munized at 3 weeks of age, IgE antibodies were produced at an early stage, but IgM and IgG antibodies were only produced at a late stage. However, when mice were immu nized at 4 weeks of age, not only IgE but also IgM and IgG production took the pat terns similar to those in adult mice. There fore, in the process of ontogcnic develop ment, the capacity to produce IgE antibod ies appears to mature earlier than that to produce IgM and IgG antibodies. Wigzell and Stjernsward [14] reported that direct plaque-forming cells were detect able after immunization with sheep red blood cells in 7-day-old mice. Takeya and Nomoto [15] reported that 2-ME-sensitive antibodies were produced on day 10 after immunization with sheep red blood cells in 3-day-old mice. These results suggest that the capacity to produce IgM antibodies ap pears at a younger age than 2 or 3 weeks. This discrepancy may be due to differences in antigens.
12 König, W.; Okudaira, H„ and Ishizaka, K.: Specific binding of mouse IgE with rat mast cells. J. Immun. ! !2: 1652-1659 (1974). 13 Weir, D. M.: Handbook of experimental im munology (Blackwell, Oxford 1969). 14 Wigzell, H. and Stjernswärd, J.: Age-depen dent rise and fall of immunological reactivity in the CBA mice. J. natn. Cancer Inst. 37: 513-517 (1966).
55
15 Takeya, K. and Nomoto, K.: Characteristics of antibody response in young or thymectomized mice. J. Immun. 99: 831-836 (1967).
Correspondence to: Dr. Yoshiro Imada, Depart ment of Bacteriology, School of Medicine, Kyu shu University, 1-1, 3-Chome, Maidashi, Higashiku, Fukuoka City, 812 (Japan)
Downloaded by: University of Chicago Library 205.208.116.24 - 4/9/2018 4:01:47 PM
Ontogénie Development of IgE in Mice
