The dual phases of the response to neonatal exposure to a VH family-restricted staphylococcal B cell superantigen.
In vitro studies of several naturally occurring proteins have characterized VH family-specific B lymphocyte binding and stimulatory properties that appear analogous to those of T cell superantigens. To examine the in vivo consequences of exposure to a putative B cell superantigen, we treated neonatal BALB/c mice with a form of staphylococcal protein A (MS) devoid of Fcgamma binding activity, which retains the clan VHIII Fab binding specificity. In naive adults, about 5% of peripheral B cells and >13% of splenic IgM-secreting cells display MS binding activity, in association with high IgM and low IgG circulating anti-MS Ab titers. Neonatal exposure to MS elicited two distinct temporal phases of immune responsiveness. The early phase, representing the first approximately 5 wk of life, was associated with MS-specific B cell and T cell tolerance. Microfluorometric assays revealed that exposure caused a dramatic MS-specific B cell clonal loss in bone marrow and spleen, but levels normalized by about 3 wk of life. The late phase (>6 wk of age) was associated with spontaneous priming for MS-specific T cell responses and production of MS-specific IgG1 Abs despite long term persistently depressed in vivo and in vitro MS-specific IgM responses. In vivo challenge during the late phase induced high frequencies of MS-specific IgG-secreting cells, indicating recruitment of highly focused Ab responses that were predominantly encoded by rearrangements of the S107 family, a member of the VHIII clan. These studies document the immunodominance of the VH-restricted Fab binding site on staphylococcal protein A and demonstrate the diverse effects of a B cell superantigen on the emerging peripheral B cell compartment.
Silverman
G J
GJ
The Sam and Rose Stein Institute for Research on Aging, Department of Medicine, University of California at San Diego, La Jolla 92093-0663, USA. gsilverman@ucsd.edu
Nayak
J V
JV
Warnatz
K
K
Hajjar
F F
FF
Cary
S
S
Tighe
H
H
Curtiss
V E
VE
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D005810:Multigene Family / Q000276:immunology; D013205:Staphylococcal Protein A / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D018089:Superantigens / Q000008:administration & dosage / Q000276:immunology*
D000907:Antibodies, Bacterial; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D013205:Staphylococcal Protein A; D018089:Superantigens