Staphylococcal enterotoxin D functions as a human B cell superantigen by rescuing VH4-expressing B cells from apoptosis.
Staphylococcal enterotoxins are potent superantigens, in that they activate T cells bearing specific V beta-chain gene segments. In this study, we analyzed the capacity of staphylococcal enterotoxin D (SED) to function as a B cell superantigen. SED induced T cell-dependent polyclonal proliferation and differentiation of B cells. In the absence of T cells, SED induced survival of B cells uniquely expressing VH4 containing IgM. The mechanism of survival of VH4-expressing B cells appeared to relate to the countering of apoptosis initiated by the engagement of HLA-DR by SED. Analysis of the VH4 gene products expressed by SED-stimulated B cells revealed the usage of six of the known functional VH4 genes with a variety of different CDR3 regions, employing different DH and JH gene segments. Moreover, the sequence analysis identified a possible site for SED binding of VH4 that includes the solvent-exposed surfaces of 3' CDR2/FR3 and/or FR1. Thus, SED appears to function as a unique B cell superantigen by inducing survival of VH4-expressing B cells.
Domiati-Saad
R
R
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Attrep
J F
JF
Brezinschek
H P
HP
Cherrie
A H
AH
Karp
D R
DR
Lipsky
P E
PE
D000328:Adult; D000595:Amino Acid Sequence; D000916:Antibody Diversity; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004768:Enterotoxins / Q000494:pharmacology*; D005803:Genes, Immunoglobulin / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000494:pharmacology; D018089:Superantigens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology
D004768:Enterotoxins; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011994:Recombinant Proteins; D018089:Superantigens; C019368:enterotoxin D, Staphylococcal