# Relationships between Tfh cells, somatic hypermutation, and the development of broadly neutralizing antibodies

> **NIH NIH R01** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2020 · $450,000

## Abstract

Project Summary
Little is known about the cellular mechanisms involved in generating HIV bnAbs. BnAbs are very difficult to
develop and have traits indicative of extensive affinity maturation in germinal centers (GC). One hypothesis is
that Tfh cells in the GC are important for driving the development of HIV bnAbs. Follicular helper T cells (Tfh)
are the specialized CD4 T cells for B cell help and are necessary and limiting for GCs. (1) How do Tfh cells
enhance HIV bnAb development? Is it related to Tfh quantities and/or selective functions? (2) How is somatic
hypermutation related to the likelihood of bnAb development? GC SHM activity is necessary for bnAb
development, but is there a quantitative relationship? (3) What B cell characteristics are critical to bnAb
development? We hypothesize that bnAb development in HIV+ patients may be primarily dependent on (A)
unusual B cell repertoire features, such as glycan reactivity; (B) a particular category of B cell response; and/or
(C) overall sequence space explored by SHM.

## Key facts

- **NIH application ID:** 9923560
- **Project number:** 5R01AI124796-05
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Shane P Crotty
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,000
- **Award type:** 5
- **Project period:** 2016-06-24 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923560

## Citation

> US National Institutes of Health, RePORTER application 9923560, Relationships between Tfh cells, somatic hypermutation, and the development of broadly neutralizing antibodies (5R01AI124796-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9923560. Licensed CC0.

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