Mass, charge, and subcellular localization of a unique secretory product identified by the basophil-specific antibody BB1

J Allergy Clin Immunol. 2001 May;107(5):842-8. doi: 10.1067/mai.2001.114650.

Abstract

Background: BB1 is a basophil-specific mAb (Lab Invest 1999;79:27-38). The identity of the corresponding antigen has not been determined, but it gives a granular appearance on staining and is secreted on activation of basophils.

Objective: We sought to further characterize the basophilspecific antigen identified by BB1.

Methods: Intracellular localization was determined by flow cytometry and by immunogold labeling and electron microscopy. Physical chemical properties were investigated by gel filtration chromatography and preparative isoelectric focusing.

Results: In flow cytometry, permeabilization of cells increased immunofluorescence 100-fold, confirming the predominantly intracellular localization of the antigen. It was further localized to the secretory granules by immunoelectron microscopy. Double labeling with a CD63-specific antibody demonstrated selective binding of BB1 to the granule matrix. Gel filtration chromatography indicated that the antigen is secreted as a complex of approximately 5 x 10(6) d, which was well resolved from the 210-kd supramolecular complex containing tryptase. The antigen was degraded by pronase. Isoelectric focusing indicated a highly basic protein with an isoelectric point of 9.6.

Conclusion: With its granule localization, release on cell activation, and unique properties, the antigen identified by BB1 could be a novel mediator of allergic disease. We propose the name basogranulin for this novel basophil-specific protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / immunology*
  • Antigens, CD / analysis
  • Antigens, Surface / chemistry
  • Antigens, Surface / immunology
  • Antigens, Surface / isolation & purification*
  • Basophils / chemistry*
  • Basophils / immunology
  • Basophils / metabolism
  • Basophils / ultrastructure
  • Biotinylation
  • Blood Protein Electrophoresis
  • Cell Line
  • Chromatography, Gel
  • Cytoplasmic Granules / chemistry*
  • Cytoplasmic Granules / metabolism
  • Flow Cytometry
  • Humans
  • Hypersensitivity / metabolism
  • Immunohistochemistry
  • Inflammation / metabolism
  • Inflammation Mediators / chemistry
  • Inflammation Mediators / immunology
  • Inflammation Mediators / isolation & purification*
  • Isoelectric Focusing
  • Isoelectric Point
  • Microscopy, Electron
  • Molecular Weight
  • Platelet Membrane Glycoproteins / analysis
  • Pronase / pharmacology
  • Tetraspanin 30

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Surface
  • CD63 protein, human
  • Inflammation Mediators
  • Platelet Membrane Glycoproteins
  • Tetraspanin 30
  • Pronase