May 1, 2013

The restricted DH gene reading frame usage in the expressed human antibody repertoire is selected based upon its amino acid content

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jennifer I C BenichouYoram Louzoun

Abstract

The Ab repertoire is not uniform. Some variable, diversity, and joining genes are used more frequently than others. Nonuniform usage can result from the rearrangement process, or from selection. To study how the Ab repertoire is selected, we analyzed one part of diversity generation that cannot be driven by the rearrangement mechanism: the reading frame usage of DH genes. We have used two high-throughput sequencing methodologies, multiple subjects and advanced algorithms to measure the DH reading frame usage in the human Ab repertoire. In most DH genes, a single reading frame is used predominantly, and inverted reading frames are practically never observed. The choice of a single DH reading frame is not limited to a single position of the DH gene. Rather, each DH gene participates in rearrangements of differing CDR3 lengths, restricted to multiples of three. In nonproductive rearrangements, there is practically no reading frame bias, but there is still a striking absence of inversions. Biases in DH reading frame usage are more pronounced, but also exhibit greater interindividual variation, in IgG(+) and IgA(+) than in IgM(+) B cells. These results suggest that there are two developmental checkpoints of DH reading frame selectio...Continue Reading

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Mentioned in this Paper

Immune Response
Heparin
Valine
Peripheral Blood
Inversion Mutation Abnormality
Amino Acids, I.V. solution additive
Bone Marrow
Ficoll
Codon, Terminator
Recombination, Genetic

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