# High-resolution deconvolution of selection effects on the composition of the B cell repertoire

> **NIH NIH R35** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $483,750

## Abstract

Project Summary
The random nature of V(D)J recombination, whose primary purpose is to produce antibodies that bind a broad
range of potential targets, often inadvertently creates antibodies that recognize self antigens. Such
autoreactive antibodies are often associated with autoimmune diseases that adversely affect the wellbeing of
millions and represent a significant financial burden on society. During early development, mechanisms exist
for managing autoreactive B cells, including deletion, modification, or silencing. In the periphery, B cells
undergoing affinity maturation are subject to peripheral tolerance mechanisms to prevent acquisition of high
affinity autoreactivity. Indeed, a myriad of selection and tolerance mechanisms, spanning the entirety of the B
cell lineage from early pro-B cells to long-lived plasma cells, exert massive influence on the composition of the
human antibody repertoire. Although the repertoire-shaping effects of selection and tolerance are thought to be
quite large, we still have only a limited understanding of the ways in which B cell repertoire composition is
regulated by selection.
The long-term research focus of my laboratory is to use high-throughput sequencing to gain a more complete
understanding of the development, maturation and function of the human B cell repertoire. Continuing
technological advances, including emerging single-cell analysis techniques, allow the construction of
increasingly detailed molecular profiles for large numbers of individual cells. The extremely high resolution of
such datasets will allow study of the humoral immune system at an unprecedented level of depth and detail.
Over the next five years, we will leverage these advances to address significant knowledge gaps in the
following areas. (1) Discovery of specific features or feature patterns encoded by B cell receptors that are
selectively depleted or modified by central tolerance. (2) Identification of early B cell development checkpoints
at which selection and tolerance homogenize the repertoires of different individuals. (3) Characterization of
global patterns of affinity maturation which, independent of any particular antigen, globally shape the
composition of the memory repertoire. A more complete understanding of the processes and mechanisms that
shape the B cell repertoire is vitally important and broadly relevant to ongoing research in infectious disease,
autoimmunity, and rational vaccine development.

## Key facts

- **NIH application ID:** 9980447
- **Project number:** 5R35GM133682-02
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Bryan Briney
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $483,750
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980447

## Citation

> US National Institutes of Health, RePORTER application 9980447, High-resolution deconvolution of selection effects on the composition of the B cell repertoire (5R35GM133682-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980447. Licensed CC0.

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