Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1983 Mar 1;157(3):813–827. doi: 10.1084/jem.157.3.813

Germinal center B cells lack homing receptors necessary for normal lymphocyte recirculation

PMCID: PMC2186964  PMID: 6339668

Abstract

Germinal center B cells (GCLC) are a discrete population of antigen- activated lymphoblasts that lack surface IgD and express abundant cell surface binding sites for peanut agglutinin (PNA). These phenotypic features render GCLC easily distinguishable from nearly all plasma cells, T cells, and unstimulated B cells, and have enabled us to identify and isolate GCLC from antigen-stimulated murine lymphoid organs. We have examined the migratory properties of these lymphoblasts in (a) short-term in vivo homing studies, and (b) an in vitro assay of lymphocyte binding to post-capillary, high endothelial venules (HEV) in frozen sections of Peyer's patches and peripheral lymph nodes. In the in vivo experiments, intravenously injected GCLC failed to migrate in significant numbers to peripheral lymphoid organs in comparison with T cells or IgD+ B cells. In the in vitro binding assay, GCLC did not adhere to HEV in either Peyer's patch or peripheral node sections. A variety of factors, such as preferential sequestration in the liver, may operate in vivo to influence the localization of these cells. However, their nearly total failure to migrate into lymphoid organs can best be explained by their inability to recognize and adhere to the specialized HEV which normally mediate the emigration of recirculating lymphocytes from the blood into these sites. The concept that GCLC fail to express functional homing receptors for HEV has been further supported by studies using MEL-14, a monoclonal antibody that appears to recognize the lymphocyte surface receptor for peripheral node HEV: In contrast to most peripheral lymphocytes, GCLC fail to bind MEL-14. These migratory and endothelial-recognition properties of GCLC, when viewed in the context of the possible role of these cells as precursors of plasma cells and/or memory B cells, have led us to propose that the inability of GCLC to recognize HEV may be transient and related to a phase of sessile B cell differentiation.

Full Text

The Full Text of this article is available as a PDF (2.1 MB).

Selected References

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

  1. Ashwell G., Morell A. G. The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv Enzymol Relat Areas Mol Biol. 1974;41(0):99–128. doi: 10.1002/9780470122860.ch3. [DOI] [PubMed] [Google Scholar]
  2. Butcher E. C., Rouse R. V., Coffman R. L., Nottenburg C. N., Hardy R. R., Weissman I. L. Surface phenotype of Peyer's patch germinal center cells: implications for the role of germinal centers in B cell differentiation. J Immunol. 1982 Dec;129(6):2698–2707. [PubMed] [Google Scholar]
  3. Butcher E. C., Scollay R. G., Weissman I. L. Lymphocyte adherence to high endothelial venules: characterization of a modified in vitro assay, and examination of the binding of syngeneic and allogeneic lymphocyte populations. J Immunol. 1979 Nov;123(5):1996–2003. [PubMed] [Google Scholar]
  4. Chen L. L., Adams J. C., Steinman R. M. Anatomy of germinal centers in mouse spleen, with special reference to "follicular dendritic cells". J Cell Biol. 1978 Apr;77(1):148–164. doi: 10.1083/jcb.77.1.148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Craig S. W., Cebra J. J. Peyer's patches: an enriched source of precursors for IgA-producing immunocytes in the rabbit. J Exp Med. 1971 Jul 1;134(1):188–200. doi: 10.1084/jem.134.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ford W. L., Sedgley M., Sparshott S. M., Smith M. E. The migration of lymphocytes across specialized vascular endothelium. II. The contrasting consequences of treating lymphocytes with tryspin or neuraminidase. Cell Tissue Kinet. 1976 Jul;9(4):351–361. [PubMed] [Google Scholar]
  7. GOWANS J. L., KNIGHT E. J. THE ROUTE OF RE-CIRCULATION OF LYMPHOCYTES IN THE RAT. Proc R Soc Lond B Biol Sci. 1964 Jan 14;159:257–282. doi: 10.1098/rspb.1964.0001. [DOI] [PubMed] [Google Scholar]
  8. Gutman G. A., Weissman I. L. Lymphoid tissue architecture. Experimental analysis of the origin and distribution of T-cells and B-cells. Immunology. 1972 Oct;23(4):465–479. [PMC free article] [PubMed] [Google Scholar]
  9. Guy-Grand D., Griscelli C., Vassalli P. The gut-associated lymphoid system: nature and properties of the large dividing cells. Eur J Immunol. 1974 Jun;4(6):435–443. doi: 10.1002/eji.1830040610. [DOI] [PubMed] [Google Scholar]
  10. Harford J., Ashwell G. G. Immunological evidence for the transmembrane nature of the rat liver receptor for asialoglycoproteins. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1557–1561. doi: 10.1073/pnas.78.3.1557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jones P. P., Cebra J. J. Restriction of gene expression in B lymphocytes and their progeny. III. Endogenous IgA and IgM on the membranes of different plasma cell precursors. J Exp Med. 1974 Oct 1;140(4):966–976. doi: 10.1084/jem.140.4.966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jones P. P., Craig S. W., Cebra J. J., Herzenberg L. A. Restriction of gene expression in B lymphocytes and their progeny. II. Commitment to immunoglobulin heavy chain isotype. J Exp Med. 1974 Aug 1;140(2):452–469. doi: 10.1084/jem.140.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kelly R. H. Localization of afferent lymph cells within the draining node during a primary immune response. Nature. 1970 Aug 1;227(5257):510–513. doi: 10.1038/227510a0. [DOI] [PubMed] [Google Scholar]
  14. Klaus G. G., Kunkl A. The role of germinal centres in the generation of immunological memory. Ciba Found Symp. 1981;84:265–280. doi: 10.1002/9780470720660.ch14. [DOI] [PubMed] [Google Scholar]
  15. Kolb-Bachofen V., Schlepper-Schäfer J., Vogell W., Kolb H. Electron microscopic evidence for an asialoglycoprotein receptor on Kupffer cells: localization of lectin-mediated endocytosis. Cell. 1982 Jul;29(3):859–866. doi: 10.1016/0092-8674(82)90447-0. [DOI] [PubMed] [Google Scholar]
  16. Kolb H., Vogt D., Herbertz L., Corfield A., Schauer R., Schlepper-Schäfer J. The galactose-specific lectins on rat hepatocytes and Kupffer cells have identical binding characteristics. Hoppe Seylers Z Physiol Chem. 1980 Nov;361(11):1747–1750. [PubMed] [Google Scholar]
  17. Kraal G., Weissman I. L., Butcher E. C. Germinal centre B cells: antigen specificity and changes in heavy chain class expression. Nature. 1982 Jul 22;298(5872):377–379. doi: 10.1038/298377a0. [DOI] [PubMed] [Google Scholar]
  18. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  19. London J., Berrih S., Bach J. F. Peanut agglutinin. I. A new tool for studying T lymphocyte subpopulations. J Immunol. 1978 Aug;121(2):438–443. [PubMed] [Google Scholar]
  20. Lotan R., Skutelsky E., Danon D., Sharon N. The purification, composition, and specificity of the anti-T lectin from peanut (Arachis hypogaea). J Biol Chem. 1975 Nov 10;250(21):8518–8523. [PubMed] [Google Scholar]
  21. NOSSAL G. J., ADA G. L., AUSTIN C. M. ANTIGENS IN IMMUNITY. IV. CELLULAR LOCALIZATION OF 125-I- AND 131-I-LABELLED FLAGELLA IN LYMPH NODES. Aust J Exp Biol Med Sci. 1964 Jun;42:311–330. [PubMed] [Google Scholar]
  22. Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
  23. Opstelten D., Stikker R., Deenen G. J., Bos L., Nieuwenhuis P. Germinal centers and the B-cell system. VI. Migration pattern of germinal-center cells of the rabbit appendix. Cell Tissue Res. 1981;218(1):59–73. doi: 10.1007/BF00210091. [DOI] [PubMed] [Google Scholar]
  24. Reisner Y., Biniaminov M., Rosenthal E., Sharon N., Ramot B. Interaction of peanut agglutinin with normal human lymphocytes and with leukemic cells. Proc Natl Acad Sci U S A. 1979 Jan;76(1):447–451. doi: 10.1073/pnas.76.1.447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rose M. L., Birbeck M. S., Wallis V. J., Forrester J. A., Davies A. J. Peanut lectin binding properties of germinal centres of mouse lymphoid tissue. Nature. 1980 Mar 27;284(5754):364–366. doi: 10.1038/284364a0. [DOI] [PubMed] [Google Scholar]
  26. Rouse R. V., Ledbetter J. A., Weissman I. L. Mouse lymph node germinal centers contain a selected subset of T cells--the helper phenotype. J Immunol. 1982 May;128(5):2243–2246. [PubMed] [Google Scholar]
  27. Rowley D. A., Gowans J. L., Atkins R. C., Ford W. L., Smith M. E. The specific selection of recirculating lymphocytes by antigen in normal and preimmunized rats. J Exp Med. 1972 Sep 1;136(3):499–513. doi: 10.1084/jem.136.3.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schwartz A. L., Marshak-Rothstein A., Rup D., Lodish H. F. Identification and quantification of the rat hepatocyte asialoglycoprotein receptor. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3348–3352. doi: 10.1073/pnas.78.6.3348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Smith M. E., Martin A. F., Ford W. L. Migration of lymphoblasts in the rat. Preferential localization of DNA-synthesizing lymphocytes in particular lymph nodes and other sties. Monogr Allergy. 1980;16:203–232. [PubMed] [Google Scholar]
  30. Sordat B., Sordat M., Hess M. W., Stoner R. D., Cottier H. Specific antibody within lymphoid germinal center cells of mice after primary immunization with horseradish peroxidase: a light and electron microscopic study. J Exp Med. 1970 Jan 1;131(1):77–91. doi: 10.1084/jem.131.1.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sprent J., Miller J. F., Mitchell G. F. Antigen-induced selective recruitment of circulating lymphocytes. Cell Immunol. 1971 Apr;2(2):171–181. doi: 10.1016/0008-8749(71)90036-0. [DOI] [PubMed] [Google Scholar]
  32. Stamper H. B., Jr, Woodruff J. J. Lymphocyte homing into lymph nodes: in vitro demonstration of the selective affinity of recirculating lymphocytes for high-endothelial venules. J Exp Med. 1976 Sep 1;144(3):828–833. doi: 10.1084/jem.144.3.828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Stevens S. K., Weissman I. L., Butcher E. C. Differences in the migration of B and T lymphocytes: organ-selective localization in vivo and the role of lymphocyte-endothelial cell recognition. J Immunol. 1982 Feb;128(2):844–851. [PubMed] [Google Scholar]
  34. Tseng J. Transfer of lymphocytes of Peyer's patches between immunoglobulin allotype congenic mice: repopulation of the IgA plasma cells in the gut lamina propria. J Immunol. 1981 Nov;127(5):2039–2043. [PubMed] [Google Scholar]
  35. Williams A. F., Gowans J. L. The presence of IgA on the surface of rat thoractic duct lymphocytes which contain internal IgA. J Exp Med. 1975 Feb 1;141(2):335–345. doi: 10.1084/jem.141.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Woodruff J. J., Gesner B. M. The effect of neuraminidase on the fate of transfused lymphocytes. J Exp Med. 1969 Mar 1;129(3):551–567. doi: 10.1084/jem.129.3.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Woodruff J. J., Katz M., Lucas L. E., Stamper H. B., Jr An in vitro model of lymphocyte homing. II. Membrane and cytoplasmic events involved in lymphocyte adherence to specialized high-endothelial venules of lymph nodes. J Immunol. 1977 Nov;119(5):1603–1610. [PubMed] [Google Scholar]
  38. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES