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Paucity of Humoral Response in Patients to Glioma-Associated Antigen(s): Antigen Localization by Immunofluorescence

  • Duncan K. Fischer
  • Masafumi Matsuda
  • Fatma Shaban
  • Raj K. Narayan
  • M. Zouhair Atassi
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 303)

Abstract

Xenogeneic immunization of freshly-prepared human glioma extracts into goats has yielded a polyclonal antiserum, which after multiple absorptions specifically identifies antigenic entities only in glioma extracts, and not in appropriate controls, both by radioimmunoassays (RIAs) and Western immunoblots. The results from the absorbed polyclonal antiserum have been confirmed by the successful generation of six stable murine monoclonal antibodies (MAbs) which recognize a subset of the same antigens with high specificity on immunoblots and with no apparent cross-reactivities by RIA to normal brain, serum, liver, muscle, kidney, spleen, or melanoma tissues. Moreover, the tested murine MAbs (B12C4) reveal a striking and abundant glial filament protein, possibly related to glial fibrillary acidic protein (GFAP) or other intermediate filament proteins, by frozen-section immunofluorescence. This is seen only in gliomas and is absent, or dramatically reduced, in normal human cortex. Use of potent immortalizing strain (FF41) of Epstein-Barr virus (EBV) to establish antibody-secreting human lymphoblastoid lines, and the generation of mouse-human chimeric fusions, have yielded lines possessing variable supernatant human antibody secretion. Radioimmunoassays using culture supernatants, and sera from glioma patients and an normal individual, have demonstrated surprisingly similar reactivity profiles, even after a sensitive sandwich RIA employing the B6C6 murine MAb. These results suggest that, although human glioma-associated antigens, including possibly the up-regulation of GFAP expression, clearly exist, there seems to be a muted humoral response as evidenced by a paucity of tumor-specific B-cells. This may be due to antigenic shielding by the blood-brain barrier, or due to a form of immunological compromise in patients harboring these malignancies.

Keywords

Glial Fibrillary Acidic Protein Glioma Patient Glial Fibrillary Acidic Protein Expression Primary Central Nervous System Neoplasm Melanoma Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Duncan K. Fischer
    • 1
    • 2
  • Masafumi Matsuda
    • 1
    • 2
  • Fatma Shaban
    • 2
  • Raj K. Narayan
    • 1
  • M. Zouhair Atassi
    • 2
  1. 1.Department of NeurosurgeryBaylor College of MedicineHoustonUSA
  2. 2.Department of BiochemistryBaylor College of MedicineHoustonUSA

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