# Affinity maturation of the B-cell repertoire

> **NIH NIH P01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $360,000

## Abstract

Abstract
Influenza infection or immunization elicit robust humoral responses but mutations that
accumulate in the influenza virus hemagglutinin (HA) render both types of humoral responses
seasonal: immunity against this season's flu does not reliably protect against next year's virus.
Crucially, vaccine efficacy is influenced by each individual's history of infection and vaccination
and this influence is long-lived and can be traced to the memory B cells compartments elicited
by prior exposure to HA antigens. The immunological basis of this influence or clonal imprinting,
is clonal dominance by memory B lymphocytes generated to cross-reactive HA antigens.
Examples of clonal imprinting or original antigenic sin (OAS) have been well described, but the
scope, durability, and structural constraints of imprinting have not been systematically studied.
In project 2 we will use a novel method for large scale, single B-cell cloning to determine how
and in which immunological compartments OAS is “stored” and to define the structural
similarities of epitope and paratope necessary for imprinting. Two types of memory B cells are
responsible for the maintenance of humoral immune memory, IgM+ memory B cells (IgM+ Bmem)
that have not undergone class-switch and class-switched (e.g., IgG+) Bmem; these small,
quiescent lymphocytes reside in secondary lymphoid organs, where they are efficiently exposed
to antigens. The population structure and dynamics of these populations following exposure to
influenza hemagglutinins (HAs) is the focus of Project 2..

## Key facts

- **NIH application ID:** 10229503
- **Project number:** 5P01AI089618-10
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** GARNETT H KELSOE
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $360,000
- **Award type:** 5
- **Project period:** 2011-08-01 → 2023-04-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229503

## Citation

> US National Institutes of Health, RePORTER application 10229503, Affinity maturation of the B-cell repertoire (5P01AI089618-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10229503. Licensed CC0.

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