Age-associated changes in binding of human B lymphocytes to a VH3-restricted unconventional bacterial antigen.
We have recently demonstrated that there is a site on Staphylococcal protein A (SpA) that interacts with B cell Ig receptors in a manner comparable with known T cell superantigens, because this binding specificity is restricted to Fab with VH3 H chains and most VH3 Ig bind SpA. In the present studies, SpA was used as a phenotypic marker for VH3 expression by human lymphoid cells. As expected, this Fab-mediated binding specificity was completely inhibited by certain VH3 antibodies but not by antibodies from other VH families. In multiparameter flow cytometric analyses, this binding activity was demonstrated to be highly prevalent among B cells (14 to 54%), and was more common among IgM-bearing B cells compared with IgG-bearing B cells. In all studies, Fab-mediated binding of SpA was uniformly expressed by a greater proportion of CD5-positive B cells than CD5-negative B cells. The proportion of B lymphocytes with this VH3-restricted binding capacity was found to undergo age-associated changes, because a large proportion of the peripheral B cells of neonates (mean +/- SD, 46.0 +/- 2.9%) bind this site, but two 10-mo-old subjects and older children had significantly lower binding levels (29.0 +/- 3.5%) that were the same as binding levels by adult peripheral B lymphocytes (30.2 +/- 3.3%). In immunohistochemical studies, tonsilar B cells that bind this site on SpA were shown to be common in mantle zones and germinal centers of secondary follicles. We speculate that Fab-mediated SpA binding represents a fundamental and primitive binding capacity that is part of the human preimmune repertoire, and we discuss the implications for the observed age-dependent shift in Fab-mediated binding of SpA by peripheral blood B cells.
Silverman
G J
GJ
Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla 92093.
Sasano
M
M
Wormsley
S B
SB
D000328:Adult; D000375:Aging / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens; D002648:Child; D002675:Child, Preschool; D015321:Gene Rearrangement; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology*; D007223:Infant; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008875:Middle Aged; D013205:Staphylococcal Protein A / Q000276:immunology*
D015703:Antigens, CD; D018956:CD5 Antigens; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D013205:Staphylococcal Protein A