Sensitization with xenogeneic tissues alters the heavy chain repertoire of human anti-Galalpha1-3Gal antibodies.
BACKGROUND
Antigen sensitization alters the use of genes encoding the variable and constant regions of immunoglobulin, changing avidity, and function. Alterations in variable region genes induced by carbohydrate antigens have been studied extensively in animals but are incompletely characterized in humans. We asked how sensitization with the carbohydrate Galalpha1-3Gal modifies antibody heavy chain use.


METHODS
To overcome limited access to B cells, we analyzed anti-Galalpha1-3Gal antibodies from the serum of naïve and sensitized human subjects with anti-sera specific for VH families.


RESULTS
We find that in preimmune subjects, heavy chains of IgM anti-Galalpha1-3Gal derived primarily from VH3 family members, whereas the heavy chains of IgG are from diverse VH families. After sensitization, heavy chains of IgM and IgG antibodies both derived from diverse VH families.


CONCLUSIONS
The preimmune repertoire of IgM antibodies to Galalpha1-3Gal is thus more restricted than the antibody repertoire after sensitization, suggesting an antigen-induced shift in the repertoire.
Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
Paul B
PB
Yu
William
W
Parker
Jayakar V
JV
Nayak
Jeffrey L
JL
Platt
D000328:Adult; D000818:Animals; D000918:Antibody Specificity; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*; D014312:Trisaccharides / Q000737:chemistry
D004187:Disaccharides; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D014312:Trisaccharides; C055075:galactosyl-(1-3)galactose