Infant and adult human B cell responses to rotavirus share common immunodominant variable gene repertoires.
Ab repertoires exhibit marked restrictions during fetal life characterized by biases of variable gene usage and lack of junctional diversity. We tested the hypothesis that Ab repertoire restriction contributes to the observed poor quality of specific Ab responses made by infants to viral infections. We analyzed the molecular determinants of B cell responses in humans to two Ags of rotavirus (RV), a common and clinically important infection of human infants. We sequenced Ab H and L chain V region genes (V(H) and V(L)) of clones expanded from single B cells responding to RV virus protein 6 or virus protein 7. We found that adults exhibited a distinct bias in use of gene segments in the V(H)1 and V(H)4 families, for example, V(H)1-46, V(H)4-31, and V(H)4-61. This gene segment bias differed markedly from the V(H)3 dominant bias seen in randomly selected adult B cells. Recombinant Abs incorporating any of those three immunodominant V(H) segments bound to RV-infected cells and also to purified RV particles. The RV-specific B cell repertoires of infants aged 2-11 mo and those of adults were highly related when compared by V(H), D, J(H), V(L), and J(L) segment selection, extent of junctional diversity, and mean H chain complementarity determining region 3 length. These data suggest that residual fetal bias of the B cell repertoire is not a limiting determinant of the quality of Ab responses to viruses of infants beyond the neonatal period.
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232-2581, USA.
Jörn-Hendrik
JH
Weitkamp
Nicole
N
Kallewaard
Koichi
K
Kusuhara
Elizabeth
E
Bures
John V
JV
Williams
Bonnie
B
LaFleur
Harry B
HB
Greenberg
James E
JE
Crowe
D000328:Adult; D000916:Antibody Diversity / Q000235:genetics; D000918:Antibody Specificity / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D016056:Immunodominant Epitopes / Q000096:biosynthesis / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D007144:Immunoglobulin J-Chains / Q000096:biosynthesis / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics*; D007223:Infant; D018655:Lymphocyte Count; D008297:Male; D017434:Protein Structure, Tertiary / Q000235:genetics; D011897:Random Allocation; D012401:Rotavirus / Q000276:immunology*
D022801:Complementarity Determining Regions; D016056:Immunodominant Epitopes; D007143:Immunoglobulin Heavy Chains; D007144:Immunoglobulin J-Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region