Gallium arsenide exposure impairs splenic B cell accessory function.
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.
Gondre-Lewis
Timothy A
TA
Department of Microbiology and Immunology, Medicine Science Bldg., 1217 East Marshall St., Rm. 229, Richmond, VA 23298, USA.
Hartmann
Constance B
CB
Caffrey
Rebecca E
RE
McCoy
Kathleen L
KL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation / Q000187:drug effects; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001152:Arsenicals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D015153:Blotting, Western; D002403:Cathepsins / Q000096:biosynthesis / Q000378:metabolism; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005708:Gallium / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D005802:Genes, MHC Class II / Q000235:genetics; D007111:Immunity, Cellular / Q000187:drug effects*; D051379:Mice; D013154:Spleen / Q000166:cytology* / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D000941:Antigens; D001152:Arsenicals; C043055:gallium arsenide; D005708:Gallium; D002403:Cathepsins; D010450:Endopeptidases