Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1996 Sep 1;184(3):1083–1091. doi: 10.1084/jem.184.3.1083

T helper cells in murine germinal centers are antigen-specific emigrants that downregulate Thy-1

PMCID: PMC2192770  PMID: 9064325

Abstract

After immunization, activated splenic T cells proliferate in periarteriolar lymphoid sheaths (PALS) and subsequently migrate to the lymphoid follicle where they enter nascent germinal centers. Analysis of TCR V(D)J gene rearrangements indicates extensive emigration, frequently involving more than a single white pulp region. These migrants constitute a unique set of T helper cells that express antigen- specific alpha beta TCR, CD3, and CD4, but little or no Thy-1, a differentiation antigen present on the great majority of peripheral murine T lymphocytes. The origin of CD4+ Thy-1 follicular T cells appears to be the Thy+ population in the PALS, as both sets commonly share identical V(D)J rearrangements.

Full Text

The Full Text of this article is available as a PDF (4.8 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abo T., Balch C. M. A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol. 1981 Sep;127(3):1024–1029. [PubMed] [Google Scholar]
  2. Banchereau J., Bazan F., Blanchard D., Brière F., Galizzi J. P., van Kooten C., Liu Y. J., Rousset F., Saeland S. The CD40 antigen and its ligand. Annu Rev Immunol. 1994;12:881–922. doi: 10.1146/annurev.iy.12.040194.004313. [DOI] [PubMed] [Google Scholar]
  3. Bowen M. B., Butch A. W., Parvin C. A., Levine A., Nahm M. H. Germinal center T cells are distinct helper-inducer T cells. Hum Immunol. 1991 May;31(1):67–75. doi: 10.1016/0198-8859(91)90050-j. [DOI] [PubMed] [Google Scholar]
  4. Cochet M., Pannetier C., Regnault A., Darche S., Leclerc C., Kourilsky P. Molecular detection and in vivo analysis of the specific T cell response to a protein antigen. Eur J Immunol. 1992 Oct;22(10):2639–2647. doi: 10.1002/eji.1830221025. [DOI] [PubMed] [Google Scholar]
  5. Durie F. H., Foy T. M., Masters S. R., Laman J. D., Noelle R. J. The role of CD40 in the regulation of humoral and cell-mediated immunity. Immunol Today. 1994 Sep;15(9):406–411. doi: 10.1016/0167-5699(94)90269-0. [DOI] [PubMed] [Google Scholar]
  6. Epstein M. M., Di Rosa F., Jankovic D., Sher A., Matzinger P. Successful T cell priming in B cell-deficient mice. J Exp Med. 1995 Oct 1;182(4):915–922. doi: 10.1084/jem.182.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Foy T. M., Laman J. D., Ledbetter J. A., Aruffo A., Claassen E., Noelle R. J. gp39-CD40 interactions are essential for germinal center formation and the development of B cell memory. J Exp Med. 1994 Jul 1;180(1):157–163. doi: 10.1084/jem.180.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fuller K. A., Kanagawa O., Nahm M. H. T cells within germinal centers are specific for the immunizing antigen. J Immunol. 1993 Nov 1;151(9):4505–4512. [PubMed] [Google Scholar]
  9. Galibert L., Burdin N., de Saint-Vis B., Garrone P., Van Kooten C., Banchereau J., Rousset F. CD40 and B cell antigen receptor dual triggering of resting B lymphocytes turns on a partial germinal center phenotype. J Exp Med. 1996 Jan 1;183(1):77–85. doi: 10.1084/jem.183.1.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gunter K. C., Malek T. R., Shevach E. M. T cell-activating properties of an anti-Thy-1 monoclonal antibody. Possible analogy to OKT3/Leu-4. J Exp Med. 1984 Mar 1;159(3):716–730. doi: 10.1084/jem.159.3.716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Han S., Hathcock K., Zheng B., Kepler T. B., Hodes R., Kelsoe G. Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers. J Immunol. 1995 Jul 15;155(2):556–567. [PubMed] [Google Scholar]
  12. Harriman G. R., Lycke N. Y., Elwood L. J., Strober W. T lymphocytes that express CD4 and the alpha beta-T cell receptor but lack Thy-1. Preferential localization in Peyer's patches. J Immunol. 1990 Oct 15;145(8):2406–2414. [PubMed] [Google Scholar]
  13. Hayakawa K., Hardy R. R. Murine CD4+ T cell subsets defined. J Exp Med. 1988 Nov 1;168(5):1825–1838. doi: 10.1084/jem.168.5.1825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Heath S. L., Tew J. G., Tew J. G., Szakal A. K., Burton G. F. Follicular dendritic cells and human immunodeficiency virus infectivity. Nature. 1995 Oct 26;377(6551):740–744. doi: 10.1038/377740a0. [DOI] [PubMed] [Google Scholar]
  15. Hedrick S. M., Engel I., McElligott D. L., Fink P. J., Hsu M. L., Hansburg D., Matis L. A. Selection of amino acid sequences in the beta chain of the T cell antigen receptor. Science. 1988 Mar 25;239(4847):1541–1544. doi: 10.1126/science.2832942. [DOI] [PubMed] [Google Scholar]
  16. Holmes K. L., Morse H. C., 3rd, Makino M., Hardy R. R., Hayakawa K. A unique subset of normal murine CD4+ T cells lacking Thy-1 is expanded in a murine retrovirus-induced immunodeficiency syndrome, MAIDS. Eur J Immunol. 1990 Dec;20(12):2783–2787. doi: 10.1002/eji.1830201237. [DOI] [PubMed] [Google Scholar]
  17. Jacob J., Kassir R., Kelsoe G. In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. I. The architecture and dynamics of responding cell populations. J Exp Med. 1991 May 1;173(5):1165–1175. doi: 10.1084/jem.173.5.1165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jacob J., Kelsoe G. In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. II. A common clonal origin for periarteriolar lymphoid sheath-associated foci and germinal centers. J Exp Med. 1992 Sep 1;176(3):679–687. doi: 10.1084/jem.176.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jacobson E. B., Caporale L. H., Thorbecke G. J. Effect of thymus cell injections on germinal center formation in lymphoid tissues of nude (thymusless) mice. Cell Immunol. 1974 Sep;13(3):416–430. doi: 10.1016/0008-8749(74)90261-5. [DOI] [PubMed] [Google Scholar]
  20. Kearney E. R., Pape K. A., Loh D. Y., Jenkins M. K. Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo. Immunity. 1994 Jul;1(4):327–339. doi: 10.1016/1074-7613(94)90084-1. [DOI] [PubMed] [Google Scholar]
  21. Kelsoe G. In situ studies of the germinal center reaction. Adv Immunol. 1995;60:267–288. doi: 10.1016/s0065-2776(08)60587-8. [DOI] [PubMed] [Google Scholar]
  22. Kelsoe G., Zheng B. Sites of B-cell activation in vivo. Curr Opin Immunol. 1993 Jun;5(3):418–422. doi: 10.1016/0952-7915(93)90062-w. [DOI] [PubMed] [Google Scholar]
  23. Kroczek R. A., Gunter K. C., Seligmann B., Shevach E. M. Induction of T cell activation by monoclonal anti-Thy-1 antibodies. J Immunol. 1986 Jun 15;136(12):4379–4384. [PubMed] [Google Scholar]
  24. Lenschow D. J., Walunas T. L., Bluestone J. A. CD28/B7 system of T cell costimulation. Annu Rev Immunol. 1996;14:233–258. doi: 10.1146/annurev.immunol.14.1.233. [DOI] [PubMed] [Google Scholar]
  25. Linsley P. S., Ledbetter J. A. The role of the CD28 receptor during T cell responses to antigen. Annu Rev Immunol. 1993;11:191–212. doi: 10.1146/annurev.iy.11.040193.001203. [DOI] [PubMed] [Google Scholar]
  26. Linsley P. S., Wallace P. M., Johnson J., Gibson M. G., Greene J. L., Ledbetter J. A., Singh C., Tepper M. A. Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science. 1992 Aug 7;257(5071):792–795. doi: 10.1126/science.1496399. [DOI] [PubMed] [Google Scholar]
  27. Low M. G., Kincade P. W. Phosphatidylinositol is the membrane-anchoring domain of the Thy-1 glycoprotein. Nature. 1985 Nov 7;318(6041):62–64. doi: 10.1038/318062a0. [DOI] [PubMed] [Google Scholar]
  28. McHeyzer-Williams M. G., Davis M. M. Antigen-specific development of primary and memory T cells in vivo. Science. 1995 Apr 7;268(5207):106–111. doi: 10.1126/science.7535476. [DOI] [PubMed] [Google Scholar]
  29. Miller C., Stedra J., Kelsoe G., Cerny J. Facultative role of germinal centers and T cells in the somatic diversification of IgVH genes. J Exp Med. 1995 Apr 1;181(4):1319–1331. doi: 10.1084/jem.181.4.1319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  31. Muller-Sieburg C. E., Whitlock C. A., Weissman I. L. Isolation of two early B lymphocyte progenitors from mouse marrow: a committed pre-pre-B cell and a clonogenic Thy-1-lo hematopoietic stem cell. Cell. 1986 Feb 28;44(4):653–662. doi: 10.1016/0092-8674(86)90274-6. [DOI] [PubMed] [Google Scholar]
  32. Phillips J. A., Romball C. G., Hobbs M. V., Ernst D. N., Shultz L., Weigle W. O. CD4+ T cell activation and tolerance induction in B cell knockout mice. J Exp Med. 1996 Apr 1;183(4):1339–1344. doi: 10.1084/jem.183.4.1339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Powrie F., Coffman R. L. Cytokine regulation of T-cell function: potential for therapeutic intervention. Immunol Today. 1993 Jun;14(6):270–274. doi: 10.1016/0167-5699(93)90044-L. [DOI] [PubMed] [Google Scholar]
  34. Presky D. H., Low M. G., Shevach E. M. Role of phosphatidylinositol-anchored proteins in T cell activation. J Immunol. 1990 Feb 1;144(3):860–868. [PubMed] [Google Scholar]
  35. Reif A. E., Allen J. M. Mouse thymic iso-antigens. Nature. 1966 Jan 29;209(5022):521–523. doi: 10.1038/209521b0. [DOI] [PubMed] [Google Scholar]
  36. Reiser H., Oettgen H., Yeh E. T., Terhorst C., Low M. G., Benacerraf B., Rock K. L. Structural characterization of the TAP molecule: a phosphatidylinositol-linked glycoprotein distinct from the T cell receptor/T3 complex and Thy-1. Cell. 1986 Nov 7;47(3):365–370. doi: 10.1016/0092-8674(86)90593-3. [DOI] [PubMed] [Google Scholar]
  37. Reth M. Antigen receptors on B lymphocytes. Annu Rev Immunol. 1992;10:97–121. doi: 10.1146/annurev.iy.10.040192.000525. [DOI] [PubMed] [Google Scholar]
  38. Ronchese F., Hausmann B., Hubele S., Lane P. Mice transgenic for a soluble form of murine CTLA-4 show enhanced expansion of antigen-specific CD4+ T cells and defective antibody production in vivo. J Exp Med. 1994 Mar 1;179(3):809–817. doi: 10.1084/jem.179.3.809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Seder R. A., Paul W. E. Acquisition of lymphokine-producing phenotype by CD4+ T cells. Annu Rev Immunol. 1994;12:635–673. doi: 10.1146/annurev.iy.12.040194.003223. [DOI] [PubMed] [Google Scholar]
  40. Sentman C. L., Kumar V., Koo G., Bennett M. Effector cell expression of NK1.1, a murine natural killer cell-specific molecule, and ability of mice to reject bone marrow allografts. J Immunol. 1989 Mar 15;142(6):1847–1853. [PubMed] [Google Scholar]
  41. Shlomchik M., Mascelli M., Shan H., Radic M. Z., Pisetsky D., Marshak-Rothstein A., Weigert M. Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med. 1990 Jan 1;171(1):265–292. doi: 10.1084/jem.171.1.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sprent J. Role of H-2 gene products in the function of T helper cells from normal and chimeric mice in vivo. Immunol Rev. 1978;42:108–137. doi: 10.1111/j.1600-065x.1978.tb00260.x. [DOI] [PubMed] [Google Scholar]
  43. Staunton D. E., Thorley-Lawson D. A. Molecular cloning of the lymphocyte activation marker Blast-1. EMBO J. 1987 Dec 1;6(12):3695–3701. doi: 10.1002/j.1460-2075.1987.tb02703.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Stedra J., Cerny J. Distinct pathways of B cell differentiation. I. Residual T cells in athymic mice support the development of splenic germinal centers and B cell memory without an induction of antibody. J Immunol. 1994 Feb 15;152(4):1718–1726. [PubMed] [Google Scholar]
  45. Van den Eertwegh A. J., Noelle R. J., Roy M., Shepherd D. M., Aruffo A., Ledbetter J. A., Boersma W. J., Claassen E. In vivo CD40-gp39 interactions are essential for thymus-dependent humoral immunity. I. In vivo expression of CD40 ligand, cytokines, and antibody production delineates sites of cognate T-B cell interactions. J Exp Med. 1993 Nov 1;178(5):1555–1565. doi: 10.1084/jem.178.5.1555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Weinstein P. D., Schweitzer P. A., Cebra-Thomas J. A., Cebra J. J. Molecular genetic features reflecting the preference for isotype switching to IgA expression by Peyer's patch germinal center B cells. Int Immunol. 1991 Dec;3(12):1253–1263. doi: 10.1093/intimm/3.12.1253. [DOI] [PubMed] [Google Scholar]
  47. Weiss A., Littman D. R. Signal transduction by lymphocyte antigen receptors. Cell. 1994 Jan 28;76(2):263–274. doi: 10.1016/0092-8674(94)90334-4. [DOI] [PubMed] [Google Scholar]
  48. Winoto A., Urban J. L., Lan N. C., Goverman J., Hood L., Hansburg D. Predominant use of a V alpha gene segment in mouse T-cell receptors for cytochrome c. Nature. 1986 Dec 18;324(6098):679–682. doi: 10.1038/324679a0. [DOI] [PubMed] [Google Scholar]
  49. Zheng B., Xue W., Kelsoe G. Locus-specific somatic hypermutation in germinal centre T cells. Nature. 1994 Dec 8;372(6506):556–559. doi: 10.1038/372556a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES