RT Journal Article
ID 70dcd45d376f200a
A1 Schroeder, Jr., Harry W.
A1 Zemlin, Michael
A1 Khass, Mohamed
A1 Nguyen, Huan H.
A1 Schelonka, Robert L.
T1 Genetic Control of DH Reading Frame and Its Effect on B-Cell Development and Antigen-Specifc Antibody Production
JF Critical Reviews™ in Immunology
JO CRI
YR 2010
FD 2010-07-21
VO 30
IS 4
SP 327
OP 344
K1 immunoglobulin
K1 diversity gene segment
K1 antibody repertoire
K1 B-cell development
AB The power of the adaptive immune system to identify novel antigens depends on the ability of lymphocytes to create antigen receptors with diverse antigen-binding sites. For immunoglobulins, CDR (complementarity-determining region)-H3 lies at the center of the antigen-binding site, where it often plays a key role in antigen binding. It is created de novo by VDJ rearrangement and is thus the focus for rearrangement-dependent diversity. CDR-H3 is biased for the inclusion of tyrosine. In seeking to identify the mechanisms controlling CDR-H3 amino acid content, we observed that the coding sequence of DH gene segments demonstrate conservation of reading frame (RF)-specific sequence motifs, with RF1 enriched for tyrosine and depleted of hydrophobic and charged amino acids. Use of DH RF1 in functional VDJ transcripts is preferred from the earliest stages of B-cell development, "pushing" CDR-H3 to include specific categories of tyrosine-enriched antigen-binding sites. With development and maturation, the composition of the CDR-H3 repertoire appears to be “pulled” into a more refined specific range. Forcing the use of alternative DH RFs by means of gene targeting alters the expressed repertoire, enriching alternative sequence categories. This change in the repertoire variably affects antibody production and the development of specific B-cell subsets.
PB Begell House
LK https://www.dl.begellhouse.com/journals/2ff21abf44b19838,2a2a299c5ed1858d,70dcd45d376f200a.html