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. 1974 Oct 31;140(5):1285–1302. doi: 10.1084/jem.140.5.1285

ONTOGENY OF B-LYMPHOCYTE FUNCTION

I. Restricted Heterogeneity of the Antibody Response of B Lymphocytes from Neonatal and Fetal Mice

Edmond A Goidl 1, Gregory W Siskind 1
PMCID: PMC2139717  PMID: 4138468

Abstract

The ontogeny of the ability of B lymphocytes to produce an antihapten response which is heterogeneous with respect to affinity for the antigenic determinant was studied in a cell transfer system. The heterogeneity of affinity of the immune response of lethally irradiated mice reconstituted with syngeneic, adult thymus cells and fetal or neonatal tissues as a source of B lymphocytes was studied. It was found that B cells from 17 day fetal liver or neonatal liver are highly restricted with respect to heterogeneity of affinity as compared with adult spleen or bone marrow. The B-cell population achieves an adult character with respect to heterogeneity of affinity by 2 wk of age. The peripheral lymphoid tissues (spleen) appear to mature in this respect more rapidly than do central lymphoid tissues (bone marrow). Spleens from 10-day old donors behave in an adult, heterogeneous manner while bone marrow from the same donors exhibit a marked restriction in heterogeneity of affinity. Germfree mice produce an immune response which is indistinguishable from conventionally reared adult animals with respect to heterogeneity of affinity. The earlier appearance of the ability to transfer a heterogeneous immune response in spleen as compared with bone marrow suggests that the increasing heterogeneity of the B-lymphocyte population which occurs between birth and 2 wk of age is the result of a differentiation event and not of a somatic mutation or recombination event.

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Selected References

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  1. Andersson B. Studies on antibody affinity at the cellular level. Correlation between binding properties of secreted antibody and cellular receptor for antigen on immunological memory cells. J Exp Med. 1972 Feb 1;135(2):312–322. doi: 10.1084/jem.135.2.312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andersson B. Studies on the regulation of avidity at the level of the single antibody-forming cell. The effect of antigen dose and time after immunization. J Exp Med. 1970 Jul 1;132(1):77–88. doi: 10.1084/jem.132.1.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Bhargava T. N., Doyle P. H. A geometric study of diversity. J Theor Biol. 1974 Feb;43(2):241–251. doi: 10.1016/s0022-5193(74)80057-3. [DOI] [PubMed] [Google Scholar]
  5. Claflin L., Merchant B., Inman J. Antibody-binding characteristics at the cellular level. I. Comparative maturation of hapten-specific IgM and IgG plaque-forming cell populations. J Immunol. 1973 Jan;110(1):241–251. [PubMed] [Google Scholar]
  6. Davie J. M., Paul W. E., Asofsky R., Warren R. W. Ontogeny of immunoglobulin-bearing lymphocytes and DNP-specific antigen-binding cells in guinea pigs. J Immunol. 1974 Jun;112(6):2202–2209. [PubMed] [Google Scholar]
  7. Davie J. M., Paul W. E. Receptors on immunocompetent cells. V. Cellular correlates of the "maturation" of the immune response. J Exp Med. 1972 Mar 1;135(3):660–674. doi: 10.1084/jem.135.3.660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. EISEN H. N., SISKIND G. W. VARIATIONS IN AFFINITIES OF ANTIBODIES DURING THE IMMUNE RESPONSE. Biochemistry. 1964 Jul;3:996–1008. doi: 10.1021/bi00895a027. [DOI] [PubMed] [Google Scholar]
  9. Fujio H., Karush F. Antibody affinity. II. Effect of immunization interval on antihapten antibody in the rabbit. Biochemistry. 1966 Jun;5(6):1856–1863. doi: 10.1021/bi00870a011. [DOI] [PubMed] [Google Scholar]
  10. Gelfand M. C., Elfenbein G. J., Frank M. M., Paul W. E. Ontogeny of B lymphocytes. II. Relative rates of appearance of lymphocytes bearing surface immunoglobulin and complement receptors. J Exp Med. 1974 May 1;139(5):1125–1141. doi: 10.1084/jem.139.5.1125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goidl E. A., Paul W. E., Siskind G. W., Benacerraf B. The effect of antigen dose and time after immunization on the amount and affinity of anti-hapten antibody. J Immunol. 1968 Feb;100(2):371–375. [PubMed] [Google Scholar]
  12. Huchet R., Feldmann M. Studies on antibody affinity in mice. Eur J Immunol. 1973 Jan;3(1):49–55. doi: 10.1002/eji.1830030111. [DOI] [PubMed] [Google Scholar]
  13. JANDL J. H., SIMMONS R. L. The agglutination and sensitization of red cells by metallic cations: interactions between multivalent metals and the red-cell membrane. Br J Haematol. 1957 Jan;3(1):19–38. doi: 10.1111/j.1365-2141.1957.tb05768.x. [DOI] [PubMed] [Google Scholar]
  14. Kim Y. T., Siskind G. W. Studies on the control of antibody synthesis. VI. Effect of antigen dose and time after immunization on antibody affinity and heterogeneity in the mouse. Clin Exp Immunol. 1974 Jun;17(2):329–338. [PMC free article] [PubMed] [Google Scholar]
  15. Klinman N. R. Antibody with homogeneous antigen binding produced by splenic foci in organ culture. Immunochemistry. 1969 Sep;6(5):757–759. doi: 10.1016/0019-2791(67)90140-1. [DOI] [PubMed] [Google Scholar]
  16. Lamelin J. P., Paul W. E. Rate of increase of antibody affinity in different rat strains. Int Arch Allergy Appl Immunol. 1971;40(3):351–360. doi: 10.1159/000230418. [DOI] [PubMed] [Google Scholar]
  17. Levin H. A., Levine H., Schlossman S. F. Antigen recognition and antibody specificity. Carrier specificity and genetic control of anti-dinitrophenyl-oligolysine antibody. J Exp Med. 1971 Jun 1;133(6):1199–1218. doi: 10.1084/jem.133.6.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miller G. W., Segre D. Determination of relative affinity and heterogeneity of mouse anti-DNP antibodies by a plaque-inhibition technique. J Immunol. 1972 Jul;109(1):74–83. [PubMed] [Google Scholar]
  19. Montgomery P. C., Williamson A. R. Molecular restriction of anti-hapten antibody elicited in neonatal rabbits. Nature. 1970 Dec 26;228(5278):1306–1308. doi: 10.1038/2281306a0. [DOI] [PubMed] [Google Scholar]
  20. Montgomery P. C., Williamson A. R. Molecular restriction of anti-hapten antibody elicited in neonatal rabbits: antibody production in littermates. J Immunol. 1972 Nov;109(5):1036–1045. [PubMed] [Google Scholar]
  21. Parker C. W., Godt S. M., Johnson M. C. Fluorescent probes for the study of the antibody-hapten reaction. II. Variation in te antibody combining site during the immune response. Biochemistry. 1967 Nov;6(11):3417–3427. doi: 10.1021/bi00863a012. [DOI] [PubMed] [Google Scholar]
  22. Pirofsky B., Davies G. H., Ramirez-Mateos J. C., Newton B. W. Cellular immune competence in the human fetus. Cell Immunol. 1973 Feb;6(2):324–328. doi: 10.1016/0008-8749(73)90032-4. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Sarvas H., Mäkelä O. Haptenated bacteriophage in the assay of antibody quantity and affinity: maturation of an immune response. Immunochemistry. 1970 Nov;7(11):933–943. doi: 10.1016/0019-2791(70)90054-6. [DOI] [PubMed] [Google Scholar]
  25. Siskind G. W., Benacerraf B. Cell selection by antigen in the immune response. Adv Immunol. 1969;10:1–50. doi: 10.1016/s0065-2776(08)60414-9. [DOI] [PubMed] [Google Scholar]
  26. Siskind G. W., Dunn P., Walker J. G. Studies on the control of antibody synthesis. II. Effect of antigen dose and of suppression by passive antibody on the affinity of antibody synthesized. J Exp Med. 1968 Jan 1;127(1):55–66. doi: 10.1084/jem.127.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Spear P. G., Edelman G. M. Maturation of the humoral immune response in mice. J Exp Med. 1974 Feb 1;139(2):249–263. doi: 10.1084/jem.139.2.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. Stutman O., Good R. A. Immunocompetence of embryonic hemopoietic cells after traffic to thymus. Transplant Proc. 1971 Mar;3(1):923–925. [PubMed] [Google Scholar]
  31. Tyan M. L., Herzenberg L. A. Studies on the ontogeny of the mouse immune system. II. Immunoglobulin-producing cells. J Immunol. 1968 Sep;101(3):446–450. [PubMed] [Google Scholar]
  32. Werblin T. P., Kim Y. T., Mage R., Benacerraf B., Siskind G. W. The generation of antibody diversity. I. Studies on the population distribution of anti-DNP antibody affinities and on the influence of allotype on antibody affinity and concentration. Immunology. 1973 Jul;25(1):17–32. [PMC free article] [PubMed] [Google Scholar]
  33. Werblin T. P., Kim Y. T., Quagliata F., Siskind G. W. Studies on the control of antibody synthesis. 3. Changes in heterogeneity of antibody affinity during the course of the immune response. Immunology. 1973 Mar;24(3):477–492. [PMC free article] [PubMed] [Google Scholar]
  34. Werblin T. P., Siskind G. W. Effect of tolerance and immunity on antibody affinity. Transplant Rev. 1972;8:104–136. doi: 10.1111/j.1600-065x.1972.tb01566.x. [DOI] [PubMed] [Google Scholar]

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