Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1996 Jan 1;183(1):227–236. doi: 10.1084/jem.183.1.227

Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow fibroblasts

PMCID: PMC2192413  PMID: 8551226

Abstract

Plasma cells represent the final stage of B lymphocyte differentiation. Most plasma cells in secondary lymphoid tissues live for a few days, whereas those in the lamina propria of mucosa and in bone marrow live for several weeks. To investigate the regulation of human plasma cell survival, plasma cells were isolated from tonsils according to high CD38 and low CD20 expression. Tonsillar plasma cells express CD9, CD19, CD24, CD37, CD40, CD74, and HLA-DR, but not CD10, HLA-DQ, CD28, CD56, and Fas/CD95. Although plasma cells express intracytoplasmic Bcl-2, they undergo swift apoptosis in vitro and do not respond to CD40 triggering. Bone marrow fibroblasts and rheumatoid synoviocytes, however, prevented plasma cells from undergoing apoptosis in a contact- dependent fashion. These data indicate that fibroblasts may form a microenvironment favorable for plasma cell survival under normal and pathological conditions.

Full Text

The Full Text of this article is available as a PDF (2.8 MB).

Selected References

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

  1. Anderson K. C., Bates M. P., Slaughenhoupt B. L., Pinkus G. S., Schlossman S. F., Nadler L. M. Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation. Blood. 1984 Jun;63(6):1424–1433. [PubMed] [Google Scholar]
  2. Ashall F. Genes for normal and diseased mental states. Trends Genet. 1994 Feb;10(2):37–39. doi: 10.1016/0168-9525(94)90138-4. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Banchereau J., Rousset F. Human B lymphocytes: phenotype, proliferation, and differentiation. Adv Immunol. 1992;52:125–262. doi: 10.1016/s0065-2776(08)60876-7. [DOI] [PubMed] [Google Scholar]
  5. Clark E. A., Ledbetter J. A. Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4494–4498. doi: 10.1073/pnas.83.12.4494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dechanet J., Merville P., Durand I., Banchereau J., Miossec P. The ability of synoviocytes to support terminal differentiation of activated B cells may explain plasma cell accumulation in rheumatoid synovium. J Clin Invest. 1995 Feb;95(2):456–463. doi: 10.1172/JCI117685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Defrance T., Vanbervliet B., Aubry J. P., Banchereau J. Interleukin 4 inhibits the proliferation but not the differentiation of activated human B cells in response to interleukin 2. J Exp Med. 1988 Oct 1;168(4):1321–1337. doi: 10.1084/jem.168.4.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dilosa R. M., Maeda K., Masuda A., Szakal A. K., Tew J. G. Germinal center B cells and antibody production in the bone marrow. J Immunol. 1991 Jun 15;146(12):4071–4077. [PubMed] [Google Scholar]
  9. Fernandes-Alnemri T., Litwack G., Alnemri E. S. CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. J Biol Chem. 1994 Dec 9;269(49):30761–30764. [PubMed] [Google Scholar]
  10. Garrone P., Neidhardt E. M., Garcia E., Galibert L., van Kooten C., Banchereau J. Fas ligation induces apoptosis of CD40-activated human B lymphocytes. J Exp Med. 1995 Nov 1;182(5):1265–1273. doi: 10.1084/jem.182.5.1265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gregory C. D., Edwards C. F., Milner A., Wiels J., Lipinski M., Rowe M., Tursz T., Rickinson A. B. Isolation of a normal B cell subset with a Burkitt-like phenotype and transformation in vitro with Epstein-Barr virus. Int J Cancer. 1988 Aug 15;42(2):213–220. doi: 10.1002/ijc.2910420212. [DOI] [PubMed] [Google Scholar]
  12. Harada H., Kawano M. M., Huang N., Harada Y., Iwato K., Tanabe O., Tanaka H., Sakai A., Asaoku H., Kuramoto A. Phenotypic difference of normal plasma cells from mature myeloma cells. Blood. 1993 May 15;81(10):2658–2663. [PubMed] [Google Scholar]
  13. Hardin J. A., Yamaguchi K., Sherr D. H. The role of peritoneal stromal cells in the survival of sIgM+ peritoneal B lymphocyte populations. Cell Immunol. 1995 Mar;161(1):50–60. doi: 10.1006/cimm.1995.1008. [DOI] [PubMed] [Google Scholar]
  14. Hibi T., Dosch H. M. Limiting dilution analysis of the B cell compartment in human bone marrow. Eur J Immunol. 1986 Feb;16(2):139–145. doi: 10.1002/eji.1830160206. [DOI] [PubMed] [Google Scholar]
  15. Ho F., Lortan J. E., MacLennan I. C., Khan M. Distinct short-lived and long-lived antibody-producing cell populations. Eur J Immunol. 1986 Oct;16(10):1297–1301. doi: 10.1002/eji.1830161018. [DOI] [PubMed] [Google Scholar]
  16. Holder M. J., Liu Y. J., Defrance T., Flores-Romo L., MacLennan I. C., Gordon J. Growth factor requirements for the stimulation of germinal center B cells: evidence for an IL-2-dependent pathway of development. Int Immunol. 1991 Dec;3(12):1243–1251. doi: 10.1093/intimm/3.12.1243. [DOI] [PubMed] [Google Scholar]
  17. Jerne N. K. Idiotypic networks and other preconceived ideas. Immunol Rev. 1984 Jun;79:5–24. doi: 10.1111/j.1600-065x.1984.tb00484.x. [DOI] [PubMed] [Google Scholar]
  18. Kawano M. M., Mihara K., Huang N., Tsujimoto T., Kuramoto A. Differentiation of early plasma cells on bone marrow stromal cells requires interleukin-6 for escaping from apoptosis. Blood. 1995 Jan 15;85(2):487–494. [PubMed] [Google Scholar]
  19. Korsmeyer S. J., Shutter J. R., Veis D. J., Merry D. E., Oltvai Z. N. Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death. Semin Cancer Biol. 1993 Dec;4(6):327–332. [PubMed] [Google Scholar]
  20. Kosco M. H., Szakal A. K., Tew J. G. In vivo obtained antigen presented by germinal center B cells to T cells in vitro. J Immunol. 1988 Jan 15;140(2):354–360. [PubMed] [Google Scholar]
  21. Kozbor D., Moretta A., Messner H. A., Moretta L., Croce C. M. Tp44 molecules involved in antigen-independent T cell activation are expressed on human plasma cells. J Immunol. 1987 Jun 15;138(12):4128–4132. [PubMed] [Google Scholar]
  22. Kurosaka M., Ziff M. Immunoelectron microscopic study of the distribution of T cell subsets in rheumatoid synovium. J Exp Med. 1983 Oct 1;158(4):1191–1210. doi: 10.1084/jem.158.4.1191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lagresle C., Bella C., Daniel P. T., Krammer P. H., Defrance T. Regulation of germinal center B cell differentiation. Role of the human APO-1/Fas (CD95) molecule. J Immunol. 1995 Jun 1;154(11):5746–5756. [PubMed] [Google Scholar]
  24. Liu Y. J., Barthélémy C., de Bouteiller O., Arpin C., Durand I., Banchereau J. Memory B cells from human tonsils colonize mucosal epithelium and directly present antigen to T cells by rapid up-regulation of B7-1 and B7-2. Immunity. 1995 Mar;2(3):239–248. doi: 10.1016/1074-7613(95)90048-9. [DOI] [PubMed] [Google Scholar]
  25. Liu Y. J., Joshua D. E., Williams G. T., Smith C. A., Gordon J., MacLennan I. C. Mechanism of antigen-driven selection in germinal centres. Nature. 1989 Dec 21;342(6252):929–931. doi: 10.1038/342929a0. [DOI] [PubMed] [Google Scholar]
  26. Liu Y. J., Mason D. Y., Johnson G. D., Abbot S., Gregory C. D., Hardie D. L., Gordon J., MacLennan I. C. Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis. Eur J Immunol. 1991 Aug;21(8):1905–1910. doi: 10.1002/eji.1830210819. [DOI] [PubMed] [Google Scholar]
  27. MAKELA O., NOSSAL G. J. Autoradiographic studies on the immune response. II. DNA synthesis amongst single antibody-producing cells. J Exp Med. 1962 Jan 1;115:231–244. doi: 10.1084/jem.115.1.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Merville P., Dechanet J., Grouard G., Durand I., Banchereau J. T cell-induced B cell blasts differentiate into plasma cells when cultured on bone marrow stroma with IL-3 and IL-10. Int Immunol. 1995 Apr;7(4):635–643. doi: 10.1093/intimm/7.4.635. [DOI] [PubMed] [Google Scholar]
  29. Moreau I., Duvert V., Caux C., Galmiche M. C., Charbord P., Banchereau J., Saeland S. Myofibroblastic stromal cells isolated from human bone marrow induce the proliferation of both early myeloid and B-lymphoid cells. Blood. 1993 Oct 15;82(8):2396–2405. [PubMed] [Google Scholar]
  30. Möller P., Henne C., Leithäuser F., Eichelmann A., Schmidt A., Brüderlein S., Dhein J., Krammer P. H. Coregulation of the APO-1 antigen with intercellular adhesion molecule-1 (CD54) in tonsillar B cells and coordinate expression in follicular center B cells and in follicle center and mediastinal B-cell lymphomas. Blood. 1993 Apr 15;81(8):2067–2075. [PubMed] [Google Scholar]
  31. Nadler L. M., Anderson K. C., Marti G., Bates M., Park E., Daley J. F., Schlossman S. F. B4, a human B lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B lymphocytes. J Immunol. 1983 Jul;131(1):244–250. [PubMed] [Google Scholar]
  32. Nagata S., Suda T. Fas and Fas ligand: lpr and gld mutations. Immunol Today. 1995 Jan;16(1):39–43. doi: 10.1016/0167-5699(95)80069-7. [DOI] [PubMed] [Google Scholar]
  33. Nuñez G., Clarke M. F. The Bcl-2 family of proteins: regulators of cell death and survival. Trends Cell Biol. 1994 Nov;4(11):399–403. doi: 10.1016/0962-8924(94)90053-1. [DOI] [PubMed] [Google Scholar]
  34. Oltvai Z. N., Korsmeyer S. J. Checkpoints of dueling dimers foil death wishes. Cell. 1994 Oct 21;79(2):189–192. doi: 10.1016/0092-8674(94)90188-0. [DOI] [PubMed] [Google Scholar]
  35. Pascual V., Liu Y. J., Magalski A., de Bouteiller O., Banchereau J., Capra J. D. Analysis of somatic mutation in five B cell subsets of human tonsil. J Exp Med. 1994 Jul 1;180(1):329–339. doi: 10.1084/jem.180.1.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Pellat-Deceunynck C., Bataille R., Robillard N., Harousseau J. L., Rapp M. J., Juge-Morineau N., Wijdenes J., Amiot M. Expression of CD28 and CD40 in human myeloma cells: a comparative study with normal plasma cells. Blood. 1994 Oct 15;84(8):2597–2603. [PubMed] [Google Scholar]
  37. Reed J. C. Bcl-2 and the regulation of programmed cell death. J Cell Biol. 1994 Jan;124(1-2):1–6. doi: 10.1083/jcb.124.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Scott S., Pandolfi F., Kurnick J. T. Fibroblasts mediate T cell survival: a proposed mechanism for retention of primed T cells. J Exp Med. 1990 Dec 1;172(6):1873–1876. doi: 10.1084/jem.172.6.1873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stashenko P., Nadler L. M., Hardy R., Schlossman S. F. Expression of cell surface markers after human B lymphocyte activation. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3848–3852. doi: 10.1073/pnas.78.6.3848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Tew J. G., DiLosa R. M., Burton G. F., Kosco M. H., Kupp L. I., Masuda A., Szakal A. K. Germinal centers and antibody production in bone marrow. Immunol Rev. 1992 Apr;126:99–112. doi: 10.1111/j.1600-065x.1992.tb00633.x. [DOI] [PubMed] [Google Scholar]
  41. Trauth B. C., Klas C., Peters A. M., Matzku S., Möller P., Falk W., Debatin K. M., Krammer P. H. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science. 1989 Jul 21;245(4915):301–305. doi: 10.1126/science.2787530. [DOI] [PubMed] [Google Scholar]
  42. Vallé A., Zuber C. E., Defrance T., Djossou O., De Rie M., Banchereau J. Activation of human B lymphocytes through CD40 and interleukin 4. Eur J Immunol. 1989 Aug;19(8):1463–1467. doi: 10.1002/eji.1830190818. [DOI] [PubMed] [Google Scholar]
  43. Wang L., Miura M., Bergeron L., Zhu H., Yuan J. Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death. Cell. 1994 Sep 9;78(5):739–750. doi: 10.1016/s0092-8674(94)90422-7. [DOI] [PubMed] [Google Scholar]
  44. Westendorf J. J., Ahmann G. J., Armitage R. J., Spriggs M. K., Lust J. A., Greipp P. R., Katzmann J. A., Jelinek D. F. CD40 expression in malignant plasma cells. Role in stimulation of autocrine IL-6 secretion by a human myeloma cell line. J Immunol. 1994 Jan 1;152(1):117–128. [PubMed] [Google Scholar]

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

RESOURCES