图书馆订阅: Guest
Begell Digital Portal Begell 数字图书馆 电子图书 期刊 参考文献及会议录 研究收集
免疫学评论综述™
影响因子: 1.404 5年影响因子: 3.347 SJR: 0.706 SNIP: 0.55 CiteScore™: 2.19

ISSN 打印: 1040-8401
ISSN 在线: 2162-6472

免疫学评论综述™

DOI: 10.1615/CritRevImmunol.v30.i4.20
pages 327-344

Genetic Control of DH Reading Frame and Its Effect on B-Cell Development and Antigen-Specifc Antibody Production

Harry W. Schroeder, Jr.
Division of Clinical Immunology and Rheumatology, Departments of Medicine, Microbiology, and Genetics, University of Alabama at Birmingham,USA
Michael Zemlin
Department of Pediatrics, Philipps-University Marburg, Marburg, Germany
Mohamed Khass
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
Huan H. Nguyen
Principal Investigator, Viral Immunology Laboratory, International Vaccine Institute, Seoul, Korea
Robert L. Schelonka
Division of Neonatology, Department of Pediatrics, University of Oregon Health Sciences Center, Portland, OR, USA

ABSTRACT

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.


Articles with similar content:

G-Protein-Coupled Receptor Signaling, RGS Proteins, and Lymphocyte Function
Critical Reviews™ in Immunology, Vol.24, 2004, issue 6
John H. Kehrl
Retinoid-Regulated Gene Expression in Neural Development
Critical Reviews™ in Eukaryotic Gene Expression, Vol.7, 1997, issue 4
Margaret Clagett-Dame, Lori A. Plum
RKIP: A Governor of Intracellular Signaling
Critical Reviews™ in Oncogenesis, Vol.19, 2014, issue 6
Evelyn Schmid, Kristina Lorenz, Katharina Deiss
The Transcription Regulator Kruppel-Like Factor 4 and Its Dual Roles of Oncogene in Glioblastoma and Tumor Suppressor in Neuroblastoma
Forum on Immunopathological Diseases and Therapeutics, Vol.7, 2016, issue 1-2
Swapan K. Ray
Alterations in Gene Expression and Signal Transductions in Human Melanocytes and Melanoma Cells
Critical Reviews™ in Oncogenesis, Vol.5, 1994, issue 5
Douglas T. Yamanishi, Frank L. Meyskens, Jr.