Document Detail

Antibody repertoire development in fetal and neonatal piglets. II. Characterization of heavy chain complementarity-determining region 3 diversity in the developing fetus.
MedLine Citation:
PMID:  11120827     Owner:  NLM     Status:  MEDLINE    
Since the actual combinatorial diversity in the V(H) repertoire in fetal piglets represents <1% of the potential in mice and humans, we wondered whether 1) complementarity-determining region 3 (CDR3) diversity was also restricted; 2) CDR3 diversity changed with fetal age; and 3) to what extent CDR3 contributed to the preimmune VDJ repertoire. CDR3 spectratyping and sequence analyses of 213 CDR3s recovered from >30 fetal animals of different ages showed that >95% of VDJ diversity resulted from junctional diversity. Unlike sheep and cattle, somatic hypermutation does not contribute to the repertoire. These studies also revealed that 1) N region additions are as extensive in VDJ rearrangements recovered at 30 days as those in late term fetuses, suggesting that TdT is fully active at the onset of VDJ rearrangement; 2) nearly 90% of all rearrangement are in-frame until late gestation; 3) the oligoclonal CDR3 spectratype of 30-day fetal liver becomes polyclonal by 50 days, while this change occurs much later in spleen; 4) there is little evidence of individual variation in CDR3 spectratype or differences in spectratype among lymphoid tissues with the exception of the thymus; and 4) there is a tendency for usage of the most J(H) proximal D(H) segment (D(H)B) to decrease in older fetuses and for the longer D(H) segment to be trimmed to the same length as the shorter D(H) when used in CDR3. These findings suggest that in the fetal piglet, highly restricted combinatorial diversity and the lack of somatic mutation are compensated by early onset of TdT activity and other mechanisms that contribute to CDR3 junctional diversity.
J E Butler; P Weber; M Sinkora; J Sun; S J Ford; R K Christenson
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  165     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2000-12-21     Completed Date:  2001-01-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  6999-7010     Citation Subset:  AIM; IM    
Department of Microbiology and Iowa Interdisciplinary Immunology Program, University of Iowa, Iowa City, IA 52242, USA.
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MeSH Terms
Animals, Newborn / genetics,  growth & development,  immunology*
Antibody Diversity / genetics*
Base Sequence
Cloning, Molecular
Complementarity Determining Regions / biosynthesis,  chemistry,  genetics*
Conserved Sequence
Embryonic and Fetal Development / genetics,  immunology*
Gene Rearrangement, B-Lymphocyte, Heavy Chain
Gestational Age
Immunoglobulin Heavy Chains / biosynthesis,  chemistry,  genetics*
Liver / embryology,  immunology
Lymphoid Tissue / immunology,  metabolism
Molecular Sequence Data
Point Mutation
Polymerase Chain Reaction
Reading Frames / immunology
Thymus Gland / immunology,  metabolism
Reg. No./Substance:
0/Complementarity Determining Regions; 0/Immunoglobulin Heavy Chains

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