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The Sam and Rose Stein Institute for Research on Aging and the Theodore Gildred Cancer Center, Department of Medicine, University of California at San Diego, La Jolla, CA 92093
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 Fc
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.
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