Gallium arsenide exposure impairs splenic B cell accessory function

• Published in: International immunopharmacology 2003-03, Vol.3 (3), p.403-415
• Main Authors: Gondre-Lewis, Timothy A, Hartmann, Constance B, Caffrey, Rebecca E, McCoy, Kathleen L
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Antigen Presentation - drug effects; Antigen-Presenting Cells - drug effects; Antigen-Presenting Cells - immunology; Antigen-processing defect; Antigens - immunology; Arsenicals; B cell function; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biological and medical sciences; Blotting, Western; Cathepsins - biosynthesis; Cathepsins - metabolism; Cell Line; Chemical and industrial products toxicology. Toxic occupational diseases; Electrophoresis, Polyacrylamide Gel; Endopeptidases - metabolism; Fluorescent Antibody Technique; Gallium - toxicity; Gallium arsenide; Gene Expression Regulation - drug effects; Genes, MHC Class II - genetics; Immunity, Cellular - drug effects; Immunosuppression; Immunotoxicity; Medical sciences; Mice; Spleen - cytology; Spleen - drug effects; Spleen - immunology; Toxicology; Various organic compounds
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/S1567-5769(03)00007-9

Gallium arsenide (GaAs) is utilized in industries for its semiconductor and optical properties. Chemical exposure of animals systemically suppresses several immune functions. The ability of splenic B cells to activate antigen-specific helper CD4 + T cell hybridomas was assessed, and various aspects of antigen-presenting cell function were examined. GaAs-exposed murine B cells were impaired in processing intact soluble protein antigens, and the defect was antigen dependent. In contrast, B cells after exposure competently presented peptides to the T cells, which do not require processing. Cell surface expression of major histocompatibility complex (MHC) class II molecules and several costimulatory molecules on splenic B cells, which are critical for helper T cell activation, was not affected by chemical exposure. GaAs exposure also did not influence the stability of MHC class II heterodimers, suggesting that the defect may precede peptide exchange. GaAs-exposed B cells contained a normal level of aspartyl cathepsin activity; however, proteolytic activities of thiol cathepsins B and L were approximately half the control levels. Furthermore, two cleavage fragments of invariant chain, a molecular chaperone of MHC class II molecules, were increased in GaAs-exposed B cells, indicative of defective degradation. Thus, diminished thiol proteolytic activity in B cells may be responsible for their impaired antigen processing and invariant chain degradation, which may contribute to systemic immunosuppression caused by GaAs exposure.