Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1989 Jul;135(1):135–147.

Astrocytes and microglia in human brain share an epitope recognized by a B-lymphocyte-specific monoclonal antibody (LN-1).

D W Dickson 1, L A Mattiace 1
PMCID: PMC1880225  PMID: 2476034

Abstract

A B-lymphocyte-specific mouse monoclonal antibody, LN-1, recognizes two morphologic classes of glial cells in human brain. The nature and duration of tissue fixation and processing are critical in the detection of the two cell types. In tissue that is lightly fixed, LN-1 recognizes astrocytes. The astrocytic nature of the LN-1 reactive glial cell was confirmed by cytologic features, tissue distribution, immunoelectron microscopy, double labeling immunofluorescent microscopy, and staining of serial sections with antibodies to glial fibrillary acidic protein. In tissue that is fixed for longer periods or in Bouin's fixative, two glial cell types are recognized: astrocytes and microglia. The identity of the latter cell type as microglia was confirmed by morphologic features, tissue distribution, immunoelectron microscopy, and double staining with monoclonal antibodies or lectins to macrophage markers, including class II major histocompatibility antigens. The two cell types had different disposition in senile plaques of elderly individuals and of those with Alzheimer's disease. Astrocytes were present at the periphery of the plaques, whereas microglial cells were centrally placed, often in juxtaposition to amyloid. The results are discussed with respect to ontogeny of glial cells and the ability of monoclonal antibodies to recognize epitopes on unrelated proteins.

Full text

PDF
135

Images in this article

Selected References

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

  1. Brierley J. B., Brown A. W. The origin of lipid phagocytes in the central nervous system: I. The intrinsic microglia. J Comp Neurol. 1982 Nov 10;211(4):397–406. doi: 10.1002/cne.902110406. [DOI] [PubMed] [Google Scholar]
  2. Dickson D. W., Farlo J., Davies P., Crystal H., Fuld P., Yen S. H. Alzheimer's disease. A double-labeling immunohistochemical study of senile plaques. Am J Pathol. 1988 Jul;132(1):86–101. [PMC free article] [PubMed] [Google Scholar]
  3. Dickson D. W., Ksiezak-Reding H., Davies P., Yen S. H. A monoclonal antibody that recognizes a phosphorylated epitope in Alzheimer neurofibrillary tangles, neurofilaments and tau proteins immunostains granulovacuolar degeneration. Acta Neuropathol. 1987;73(3):254–258. doi: 10.1007/BF00686619. [DOI] [PubMed] [Google Scholar]
  4. Dickson D. W. Multinucleated giant cells in acquired immunodeficiency syndrome encephalopathy. Origin from endogenous microglia? Arch Pathol Lab Med. 1986 Oct;110(10):967–968. [PubMed] [Google Scholar]
  5. Epstein A. L., Marder R. J., Winter J. N., Fox R. I. Two new monoclonal antibodies (LN-1, LN-2) reactive in B5 formalin-fixed, paraffin-embedded tissues with follicular center and mantle zone human B lymphocytes and derived tumors. J Immunol. 1984 Aug;133(2):1028–1036. [PubMed] [Google Scholar]
  6. Esiri M. M., McGee J. O. Monoclonal antibody to macrophages (EMB/11) labels macrophages and microglial cells in human brain. J Clin Pathol. 1986 Jun;39(6):615–621. doi: 10.1136/jcp.39.6.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gebicke-Haerter P. J., Bauer J., Brenner A., Gerok W. Alpha 2-macroglobulin synthesis in an astrocyte subpopulation. J Neurochem. 1987 Oct;49(4):1139–1145. doi: 10.1111/j.1471-4159.1987.tb10004.x. [DOI] [PubMed] [Google Scholar]
  8. Hansen L. A., Armstrong D. M., Terry R. D. An immunohistochemical quantification of fibrous astrocytes in the aging human cerebral cortex. Neurobiol Aging. 1987 Jan-Feb;8(1):1–6. doi: 10.1016/0197-4580(87)90051-0. [DOI] [PubMed] [Google Scholar]
  9. Hayes G. M., Woodroofe M. N., Cuzner M. L. Microglia are the major cell type expressing MHC class II in human white matter. J Neurol Sci. 1987 Aug;80(1):25–37. doi: 10.1016/0022-510x(87)90218-8. [DOI] [PubMed] [Google Scholar]
  10. Hickey W. F., Kimura H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science. 1988 Jan 15;239(4837):290–292. doi: 10.1126/science.3276004. [DOI] [PubMed] [Google Scholar]
  11. Jordan F. L., Thomas W. E. Brain macrophages: questions of origin and interrelationship. Brain Res. 1988 Apr-Jun;472(2):165–178. doi: 10.1016/0165-0173(88)90019-7. [DOI] [PubMed] [Google Scholar]
  12. Ksiezak-Reding H., Dickson D. W., Davies P., Yen S. H. Recognition of tau epitopes by anti-neurofilament antibodies that bind to Alzheimer neurofibrillary tangles. Proc Natl Acad Sci U S A. 1987 May;84(10):3410–3414. doi: 10.1073/pnas.84.10.3410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  14. Lane D., Koprowski H. Molecular recognition and the future of monoclonal antibodies. Nature. 1982 Mar 18;296(5854):200–202. doi: 10.1038/296200a0. [DOI] [PubMed] [Google Scholar]
  15. Mannoji H., Yeger H., Becker L. E. A specific histochemical marker (lectin Ricinus communis agglutinin-1) for normal human microglia, and application to routine histopathology. Acta Neuropathol. 1986;71(3-4):341–343. doi: 10.1007/BF00688060. [DOI] [PubMed] [Google Scholar]
  16. McGeer P. L., Itagaki S., Boyes B. E., McGeer E. G. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology. 1988 Aug;38(8):1285–1291. doi: 10.1212/wnl.38.8.1285. [DOI] [PubMed] [Google Scholar]
  17. McGeer P. L., Itagaki S., McGeer E. G. Expression of the histocompatibility glycoprotein HLA-DR in neurological disease. Acta Neuropathol. 1988;76(6):550–557. doi: 10.1007/BF00689592. [DOI] [PubMed] [Google Scholar]
  18. McLean I. W., Nakane P. K. Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. J Histochem Cytochem. 1974 Dec;22(12):1077–1083. doi: 10.1177/22.12.1077. [DOI] [PubMed] [Google Scholar]
  19. Michaels J., Price R. W., Rosenblum M. K. Microglia in the giant cell encephalitis of acquired immune deficiency syndrome: proliferation, infection and fusion. Acta Neuropathol. 1988;76(4):373–379. doi: 10.1007/BF00686974. [DOI] [PubMed] [Google Scholar]
  20. Miles J. M., Chou S. M. A new immunoperoxidase marker for microglia in paraffin section. J Neuropathol Exp Neurol. 1988 Nov;47(6):579–587. doi: 10.1097/00005072-198811000-00001. [DOI] [PubMed] [Google Scholar]
  21. Perentes E., Rubinstein L. J. Non-specific binding of mouse myeloma IgM immunoglobulins by human myelin sheaths and astrocytes. A potential complication of nervous system immunoperoxidase histochemistry. Acta Neuropathol. 1986;70(3-4):284–288. doi: 10.1007/BF00686085. [DOI] [PubMed] [Google Scholar]
  22. Perry V. H., Hume D. A., Gordon S. Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience. 1985 Jun;15(2):313–326. doi: 10.1016/0306-4522(85)90215-5. [DOI] [PubMed] [Google Scholar]
  23. Sato Y., Mukai K., Watanabe S., Goto M., Shimosato Y. The AMeX method. A simplified technique of tissue processing and paraffin embedding with improved preservation of antigens for immunostaining. Am J Pathol. 1986 Dec;125(3):431–435. [PMC free article] [PubMed] [Google Scholar]
  24. Streit W. J., Graeber M. B., Kreutzberg G. W. Functional plasticity of microglia: a review. Glia. 1988;1(5):301–307. doi: 10.1002/glia.440010502. [DOI] [PubMed] [Google Scholar]
  25. Streit W. J., Kreutzberg G. W. Lectin binding by resting and reactive microglia. J Neurocytol. 1987 Apr;16(2):249–260. doi: 10.1007/BF01795308. [DOI] [PubMed] [Google Scholar]
  26. Suzuki H., Franz H., Yamamoto T., Iwasaki Y., Konno H. Identification of the normal microglial population in human and rodent nervous tissue using lectin-histochemistry. Neuropathol Appl Neurobiol. 1988 May-Jun;14(3):221–227. doi: 10.1111/j.1365-2990.1988.tb00883.x. [DOI] [PubMed] [Google Scholar]
  27. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wolozin B. L., Pruchnicki A., Dickson D. W., Davies P. A neuronal antigen in the brains of Alzheimer patients. Science. 1986 May 2;232(4750):648–650. doi: 10.1126/science.3083509. [DOI] [PubMed] [Google Scholar]
  29. Yen S. H., Crowe A., Dickson D. W. Monoclonal antibodies to Alzheimer neurofibrillary tangles. 1. Identification of polypeptides. Am J Pathol. 1985 Aug;120(2):282–291. [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES