Staphylococcal enterotoxin A induces survival of VH3-expressing human B cells by binding to the VH region with low affinity.
Staphylococcal enterotoxins (SE) are bacterial superantigens that bind to MHC class II molecules and to the V beta-chain of the TCR, and subsequently activate T cells expressing specific V beta regions. In this study, we have studied the effects of SEA on human B cell activation, and specifically the capacity of SEA to function as a B cell superantigen in vitro. We show herein that SEA failed to induce B cell proliferation and differentiation in the absence of T cells. However, SEA induced survival of B cells uniquely expressing VH3-containing IgM, independently of light chain utilization. The sequences of VH3 IgM gene products were determined and found to include a number of members of the VH3 family with a variety of different D and JH gene segments. Analysis of the sequences of VH3 gene products revealed possible sites in framework region 1 and/or framework region 3 that could be involved in SEA-mediated activation of VH3-expressing B cells. Binding studies showed that SEA interacts with the VH3 domain of Ig with low, but detectable affinity. These results indicate that SEA functions as a B cell superantigen by interacting with VH3 gene segments of Ig.
Domiati-Saad
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Department of Internal Medicine, Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas 75235-8884, USA.
Lipsky
P E
PE
D000595:Amino Acid Sequence; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D001666:Binding Sites, Antibody; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D017124:Conserved Sequence / Q000276:immunology; D004768:Enterotoxins / Q000378:metabolism / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000276:immunology; D005803:Genes, Immunoglobulin; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000494:pharmacology
D004768:Enterotoxins; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal