자료유형  

 학위논문

Control Number  

0016932191

International Standard Book Number  

9798379604479

Dewey Decimal Classification Number  

616.079

Main Entry-Personal Name  

Giguere, Sophie Stephanie Berube.

Publication, Distribution, etc. (Imprint  

[S.l.] : Harvard University., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(122 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 84-12, Section: B.

General Note  

Advisor: Batista, Facundo D. .

Dissertation Note  

Thesis (Ph.D.)--Harvard University, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약To protect against infection, antibodies must be produced at high rates, imposing significant pressure on the translational machinery of the B cells which produce them. The extent to which codon composition and the tRNA pool are adapted to protein production in animals is complex and poorly understood. Here, we identify a pattern of codon usage in antibody genes wherein some of the most heavily utilized codons lack a corresponding tRNA. Using mass spectrometry, we show that the tRNA pools of antibody-secreting cells are enriched for the post-transcriptional tRNA modification inosine (I34), which expands the decoding capacity of specific tRNAs through wobbling. Furthermore, through tRNA sequencing, we demonstrate that the expression of I34- modifiable tRNAs is increased in antibody-secreting cells. Genetic ablation of I34 eliminates the B cell compartment, demonstrating that this modification is essential. Furthermore, increased I34- dependent codon usage in the antibody variable region is associated with competitive advantages in both B cell development and entry to the long-lived cellular compartments. We conclude that the balance between the tRNA pool of a cell and the codon composition of antibody genes plays a critical role in their selection and effective expression. Our work has implications for not only the design, production, and selection of target antibodies for vaccines and therapeutics, but also more broadly, for the importance of a dynamic tRNA-codon interface in the functioning of mammalian cells.

Subject Added Entry-Topical Term  

Immunology.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Genetics.

Index Term-Uncontrolled  

Antibody production

Index Term-Uncontrolled  

Codon bias

Index Term-Uncontrolled  

B cells

Index Term-Uncontrolled  

Mammalian cells

Index Term-Uncontrolled  

Cellular compartments

Added Entry-Corporate Name  

Harvard University Medical Sciences

Host Item Entry  

Dissertations Abstracts International. 84-12B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:642721