Global characterizations of antibody repertoires
Abstract/Contents
- Abstract
- The adaptive immune system enables individuals to defend against previously un-encountered pathogens by trial and error. It does so by employing receptors, known as antibodies, whose active genetic diversification fine-tunes this defensive response. Tremendous progress has been made in understanding the mechanisms by which antibodies develop and signal activation. However, it was not until a few years ago, with the advent of affordable in-house high-throughput DNA sequencing, and our publication of whole zebrafish antibody repertoires, that any organism's antibody diversity was characterized comprehensively. In this dissertation, we demonstrate the power of this "top-down" approach to illuminate global, system-wide changes of immune receptor repertoires during organism development and immune response. Special attention is given to applying these measurements to build predictive dynamical models that elucidate the interplay between antibody-sequences and the B-cells that produce them. While we use zebrafish liberally as a model organism for these purposes, cross-species comparisons establish far more general principles of repertoire organization. We go further to evaluate the efficacy of high-throughput immune receptor sequencing to advance clinical goals by inferring which vaccines were received by human patients based on antibody-sequences obtained from whole blood afterward. Finally, we demonstrate the usefulness of single B-cell measurements to correlate antibody mutations to gene expression, thereby providing insight into how these variables co-vary system-wide. This work serves to illustrate the potential of global characterizations of antibody repertoires for providing newer and clearer pictures of immune dynamics in general.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2012 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Weinstein, Joshua Asher |
|---|---|
| Associated with | Stanford University, Biophysics Program. |
| Primary advisor | Fisher, Daniel S |
| Primary advisor | Quake, Stephen Ronald |
| Thesis advisor | Fisher, Daniel S |
| Thesis advisor | Quake, Stephen Ronald |
| Thesis advisor | Boyd, Scott, 1970- |
| Thesis advisor | Davis, Mark M |
| Advisor | Boyd, Scott, 1970- |
| Advisor | Davis, Mark M |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Joshua Asher Weinstein. |
|---|---|
| Note | Submitted to the Program in Biophysics. |
| Thesis | Ph.D. Stanford University 2012 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2012 by Joshua Asher Weinstein
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...