Abstract
The initial development and distribution of lymphocytes expressing surface IgM (sIgM) and of specific antigen-binding cells (ABC) were studied in the chicken in an attempt to gain information on the process by which B-cell diversity is generated. The antigens used were sheep erythrocytes (SE), keyhole limpet hemocyanin (KLH), and poly-L(Tyr, Glu)poly-D,L-Ala-poly-L-Lys (TGAL). The results indicate that generation of the total sIgM-positive population begins in the bursa and that specific clones of ABC develop in a fixed sequential pattern which is not influenced by either deprivation of or deliberate exposure to exogenous antigens. Cells bearing sIgM by immunofluorescence (IgM- positive cells) were detected first in the bursa on the 12th day of incubation, KLH-ABC and TGAL-ABC by the 16th day, and SE-ABC on the 18th day. The doubling time of the sIgM-positive population of bursal cells was determined to be approximately 10 h before significant antigen-independent seeding to the spleen began a few days before hatching. Clonal expansion of SE-ABC in the bursa also appeared to be antigen independent as was the initial development of SE-ABC in the blood and spleen which ceased abruptly after bursectomy at hatching. Specific ABC were observed to develop in multiple bursal follicles as small foci of ABC among the much larger total population of sIgM- positive cells within an individual follicle. Intravenously infused SE- ABC homed to the embryonic spleen but not to the bursa. The results are interpreted as favoring a hypothetical model in which individual stem cells give rise to multiple clones of B cells by a predetermined pattern of sequential expression of variable region genes.
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- Ada G. L., Byrt P. Specific inactivation of antigen-reactive cells with 125I-labelled antigen. Nature. 1969 Jun 28;222(5200):1291–1292. doi: 10.1038/2221291a0. [DOI] [PubMed] [Google Scholar]
- Albini B., Wick G. Delineation of B and T lymphoid cells in the chicken. J Immunol. 1974 Feb;112(2):444–450. [PubMed] [Google Scholar]
- Albini B., wick G. Ontogeny of lymphoid cell surface determinants in the chicken. Int Arch Allergy Appl Immunol. 1975;48(4):513–529. doi: 10.1159/000231339. [DOI] [PubMed] [Google Scholar]
- Argyris B. F. Role of macrophages in immunological maturation. J Exp Med. 1968 Sep 1;128(3):459–467. doi: 10.1084/jem.128.3.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bockman D. E., Cooper M. D. Pinocytosis by epithelium associated with lymphoid follicles in the bursa of Fabricius, appendix, and Peyer's patches. An electron microscopic study. Am J Anat. 1973 Apr;136(4):455–477. doi: 10.1002/aja.1001360406. [DOI] [PubMed] [Google Scholar]
- Braganza C. M., Stathopoulos G., Davies A. J., Elliott E. V., Kerbel R. S., Papamichail M., Holborow E. J. Lymphocyte: erythrocyte (L.E.) rosettes as indicators of the heterogeneity of lymphocytes in a variety of mammalian species. Cell. 1975 Feb;4(2):103–106. doi: 10.1016/0092-8674(75)90115-4. [DOI] [PubMed] [Google Scholar]
- Cairns J. Mutation selection and the natural history of cancer. Nature. 1975 May 15;255(5505):197–200. doi: 10.1038/255197a0. [DOI] [PubMed] [Google Scholar]
- Chiscon M. Q., Golub E. S. Functional development of the interacting cells in the immune response. I. Development of T cell and B cell function. J Immunol. 1972 May;108(5):1379–1386. [PubMed] [Google Scholar]
- Cooper M. D., Cain W. A., Van Alten P. J., Good R. A. Development and function of the immunoglobulin producing system. I. Effect of bursectomy at different stages of development on germinal centers, plasma cells, immunoglobulins and antibody production. Int Arch Allergy Appl Immunol. 1969;35(3):242–252. [PubMed] [Google Scholar]
- Cooper M. D., Payne L. N., Dent P. B., Burmester B. R., Good R. A. Pathogenesis of avian lymphoid leukosis. I. Histogenesis. J Natl Cancer Inst. 1968 Aug;41(2):373–378. [PubMed] [Google Scholar]
- Cosenza H., Köhler H. Specific inhibition of plaque formation to phosphorylcholine by antibody against antibody. Science. 1972 Jun 2;176(4038):1027–1029. doi: 10.1126/science.176.4038.1027. [DOI] [PubMed] [Google Scholar]
- Cunningham A. J. The generation of antibody diversity: its dependence on antigenic stimulation. Contemp Top Mol Immunol. 1974;3:1–26. doi: 10.1007/978-1-4684-2838-4_1. [DOI] [PubMed] [Google Scholar]
- D'Eustachio P., Edelman G. M. Frequency and avidity of specific antigen-binding cells in developing mice. J Exp Med. 1975 Nov 1;142(5):1078–1091. doi: 10.1084/jem.142.5.1078. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davie J. M., Paul W. E. Antigen-binding receptors on lymphocytes. Contemp Top Immunobiol. 1974;3:171–192. doi: 10.1007/978-1-4684-3045-5_7. [DOI] [PubMed] [Google Scholar]
- Decker J. M., Clarke J., Bradley L. M., Miller A., Sercarz E. E. Presence of antigen-binding cells for five diverse antigens at the onset of lymphoid development: lack of evidence for somatic diversification during ontogeny. J Immunol. 1974 Dec;113(6):1823–1833. [PubMed] [Google Scholar]
- Dwyer J. M., Warner N. L. Antigen binding cells in embryonic chicken bursa and thymus. Nat New Biol. 1971 Feb 17;229(7):210–211. doi: 10.1038/newbio229210a0. [DOI] [PubMed] [Google Scholar]
- GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goidl E. A., Siskind G. W. Ontogeny of B-lymphocyte function. I. Restricted heterogeneity of the antibody response of B lymphocytes from neonatal and fetal mice. J Exp Med. 1974 Nov 1;140(5):1285–1302. doi: 10.1084/jem.140.5.1285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grant J. A., Sanders B., Hood L. Partial amino acid sequences of chicken and turkey immunoglobulin light chains. Homology with mammalian lambda chains. Biochemistry. 1971 Aug 3;10(16):3123–3132. doi: 10.1021/bi00792a022. [DOI] [PubMed] [Google Scholar]
- Grossi C. E., Casali A. M., Bartoli S., Governa M., Manzoli F. A. Separation and characterization of cortical and medullary bursal lymphocytes. Eur J Immunol. 1974 Feb;4(2):150–152. doi: 10.1002/eji.1830040217. [DOI] [PubMed] [Google Scholar]
- Hudson L., Roitt I. M. Immunofluorescent detection of surface antigens specific to T and B lymphocytes in the chicken. Eur J Immunol. 1973 Feb;3(2):63–67. doi: 10.1002/eji.1830030202. [DOI] [PubMed] [Google Scholar]
- Isaković K., Petrović S., Marković B. M., Janković B. D. Natural lymphocytic rosettes in non-operated, thymectomized and bursectomized chickens. Experientia. 1974 Oct 15;30(10):1204–1205. doi: 10.1007/BF01923692. [DOI] [PubMed] [Google Scholar]
- Ivanyi J. Immunodeficiency in the chicken. I. Disparity in suppression of antibody responses to various antigens following surgical bursectomy. Immunology. 1975 Jun;28(6):1007–1013. [PMC free article] [PubMed] [Google Scholar]
- Ivanyi J., Murgatroyd L. B., Lydyard P. M. Bursal origin of bone marrow cells with competence for antibody formation. Immunology. 1972 Jul;23(1):107–111. [PMC free article] [PubMed] [Google Scholar]
- Jerne N. K. The somatic generation of immune recognition. Eur J Immunol. 1971 Jan;1(1):1–9. doi: 10.1002/eji.1830010102. [DOI] [PubMed] [Google Scholar]
- Julius M. H., Herzenberg L. A. Isolation of antigen-binding cells from unprimed mice: demonstration of antibody-forming cell precursor activity and correlation between precursor and secreted antibody avidities. J Exp Med. 1974 Oct 1;140(4):904–920. doi: 10.1084/jem.140.4.904. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kearney J. F., Lawton A. R. B lymphocyte differentiation induced by lipopolysaccharide. II. Response of fetal lymphocytes. J Immunol. 1975 Sep;115(3):677–681. [PubMed] [Google Scholar]
- Kincade P. W., Cooper M. D. Development and distribution of immunoglobulin-containing cells in the chicken. An immunofluorescent analysis using purified antibodies to mu, gamma and light chains. J Immunol. 1971 Feb;106(2):371–382. [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]
- Kincade P. W., Self K. S., Cooper M. D. Survival and function of bursa-derived cells in bursectomized chickens. Cell Immunol. 1973 Jul;8(1):93–102. doi: 10.1016/0008-8749(73)90096-8. [DOI] [PubMed] [Google Scholar]
- Klinman N. R., Press J. L. The characterization fo the B-cell repertoire specific for the 2,4-dinitrophenyl and 2,4,6-trinitrophenyl determinants in neonatal BALB/c mice. J Exp Med. 1975 May 1;141(5):1133–1146. doi: 10.1084/jem.141.5.1133. [DOI] [PMC free article] [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]
- Lawton A. R., Kincade P. W., Cooper M. D. Sequential expression of germ line genes in development of immunoglobulin class diversity. Fed Proc. 1975 Jan;34(1):33–39. [PubMed] [Google Scholar]
- Le Douarin N. M., Houssaint E., Jotereau F. V., Belo M. Origin of hemopoietic stem cells in embryonic bursa of Fabricius and bone marrow studied through interspecific chimeras. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2701–2705. doi: 10.1073/pnas.72.7.2701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lydyard P., Ivanyi J. Suppression of graft-versus-host-reactive lymphocytes by heterologous antithymus serum in vitro. Transplantation. 1971 Dec;12(6):493–499. doi: 10.1097/00007890-197112000-00014. [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]
- McGhee, Michalek S. M., Webb J., Navia J. M., Rahman A. F., Legler D. W. Effective immunity to dental caries: protection of gnotobiotic rats by local immunization with Streptococcus mutans. J Immunol. 1975 Jan;114(1 Pt 2):300–305. [PubMed] [Google Scholar]
- Mosier D. E., Johnson B. M. Ontogeny of mouse lymphocyte function. II. Development of the ability to produce antibody is modulated by T lymphocytes. J Exp Med. 1975 Jan 1;141(1):216–226. doi: 10.1084/jem.141.1.216. [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., Raff M. C., Cooper M. D. Studies on the generation of B lymphocytes in the mouse embryo. Eur J Immunol. 1976 Jul;5(7):468–473. doi: 10.1002/eji.1830050708. [DOI] [PubMed] [Google Scholar]
- Pinnas J. L., Fitch F. W. Immunologic competence of thymectomized rats to several soluble and particulate antigens. Int Arch Allergy Appl Immunol. 1966;30(3):217–230. doi: 10.1159/000229807. [DOI] [PubMed] [Google Scholar]
- Press J. L., Klinman N. R. Enumeration and analysis of antibody-forming cell precursors in the neonatal mouse. J Immunol. 1973 Sep;111(3):829–835. [PubMed] [Google Scholar]
- Press J. L., Klinman N. R. Frequency of hapten-specific B cells in neonatal and adult murine spleens. Eur J Immunol. 1974 Mar;4(3):155–159. doi: 10.1002/eji.1830040302. [DOI] [PubMed] [Google Scholar]
- Raff M. C., Megson M., Owen J. J., Cooper M. D. Early production of intracellular IgM by B-lymphocyte precursors in mouse. Nature. 1976 Jan 22;259(5540):224–226. doi: 10.1038/259224a0. [DOI] [PubMed] [Google Scholar]
- Raff M. C., Owen J. J., Cooper M. D., Lawton A. R., 3rd, Megson M., Gathings W. E. Differences in susceptibility of mature and immature mouse B lymphocytes to anti-immunoglobulin-induced immunoglobulin suppression in vitro. Possible implications for B-cell tolerance to self. J Exp Med. 1975 Nov 1;142(5):1052–1064. doi: 10.1084/jem.142.5.1052. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rowlands D. T., Jr, Blakeslee D., Angala E. Acquired immunity in opossum (Didelphis virginiana) embryos. J Immunol. 1974 Jun;112(6):2148–2153. [PubMed] [Google Scholar]
- Rusu V. M., Cooper M. D. In vivo effects of cortisone on the B cell line in chickens. J Immunol. 1975 Nov;115(5):1370–1374. [PubMed] [Google Scholar]
- Ryser J. E., Vassalli P. Mouse bone marrow lymphocytes and their differentiation. J Immunol. 1974 Sep;113(3):719–728. [PubMed] [Google Scholar]
- SILVERSTEIN A. M., UHR J. W., KRANER K. L., LUKES R. J. Fetal response to antigenic stimulus. II. Antibody production by the fetal lamb. J Exp Med. 1963 May 1;117:799–812. doi: 10.1084/jem.117.5.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schlamowitz M., Hillman K., Lichtiger B., Ahearn M. J. Preparation of IgG-binding membrane vesicles from the microvillar brush border of fetal rabbit yolk sac. J Immunol. 1975 Jul;115(1):296–302. [PubMed] [Google Scholar]
- Sherwin W. K., Rowlands D. T., Jr Determinants of the hierarchy of humoral immune responsiveness during ontogeny. J Immunol. 1975 Dec;115(6):1549–1554. [PubMed] [Google Scholar]
- Shortman K., Williams N., Adams P. The separation of different cell classes from lymphoid organs. V. Simple procedures for the removal of cell debris. Damaged cells and erythroid cells from lymphoid cell suspensions. J Immunol Methods. 1972 May;1(3):273–287. doi: 10.1016/0022-1759(72)90005-1. [DOI] [PubMed] [Google Scholar]
- Sigal N. H., Gearhart P. J., Klinman N. R. The frequency of phosphorylcholine-specific B cells in conventional and germfree BALB/C mice. J Immunol. 1975 Apr;114(4):1354–1358. [PubMed] [Google Scholar]
- Sorvari T., Sorvari R., Ruotsalainen P., Toivanen A., Toivanen P. Uptake of environmental antigens by the bursa of Fabricius. Nature. 1975 Jan 17;253(5488):217–219. doi: 10.1038/253217a0. [DOI] [PubMed] [Google Scholar]
- Spear P. G., Wang A. L., Rutishauser U., Edelman G. M. Characterization of splenic lymphoid cells in fetal and newborn mice. J Exp Med. 1973 Sep 1;138(3):557–573. doi: 10.1084/jem.138.3.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sterzl J., Silverstein A. M. Developmental aspects of immunity. Adv Immunol. 1967;6:337–459. doi: 10.1016/s0065-2776(08)60525-8. [DOI] [PubMed] [Google Scholar]
- Tao-Wiedmann T. W., Loor F., Hägg L. B. Development of surface immunoglobulins in the chicken. Immunology. 1975 May;28(5):821–830. [PMC free article] [PubMed] [Google Scholar]
- Trentin J., Wolf N., Cheng V., Fahlberg W., Weiss D., Bonhag R. Antibody production by mice repopulated with limited numbers of clones of lymphoid cell precursors. J Immunol. 1967 Jun;98(6):1326–1337. [PubMed] [Google Scholar]
- Tufveson G., Alm G. V. Ontogeny of spontaneous rosette-forming cells in the chicken. With special reference to the bursa of Fabricius. Int Arch Allergy Appl Immunol. 1975;48(4):537–546. doi: 10.1159/000231341. [DOI] [PubMed] [Google Scholar]
- Tufveson G., Bäck R., Alm G. V. Studies of the spontaneous rosette-forming cells in the bursa of Fabricius of the chicken. Int Arch Allergy Appl Immunol. 1974;46(3):393–404. doi: 10.1159/000231143. [DOI] [PubMed] [Google Scholar]
- Tufveson G. Spontaneous rosette-forming cells in the chicken. Tissue distribution, binding characteristics and bursa dependency. Int Arch Allergy Appl Immunol. 1975;49(3):310–324. doi: 10.1159/000231412. [DOI] [PubMed] [Google Scholar]
- Webb S. R., Cooper M. D. T cells can bind antigen via cytophilic IgM antibody made by B cells. J Immunol. 1973 Jul;111(1):275–277. [PubMed] [Google Scholar]
- Wigzell H., Andersson B. Cell separation on antigen-coated columns. Elimination of high rate antibody-forming cells and immunological memory cells. J Exp Med. 1969 Jan 1;129(1):23–36. doi: 10.1084/jem.129.1.23. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yung L. L., Wyn-Evans T. C., Diener E. Ontogeny of the murine immune system: development of antigen recognition and immune responsiveness. Eur J Immunol. 1973 Apr;3(4):224–228. doi: 10.1002/eji.1830030409. [DOI] [PubMed] [Google Scholar]