# The evolution of B cell selection and affinity maturation in ectotherms

> **NIH NIH F31** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $34,140

## Abstract

Project Summary/Abstract
 Affinity maturation increases the binding strength of the B cell receptor for its target antigen, and is a
fundamental mechanism affecting vaccine efficacy, autoimmune diseases, and the development of
immunotherapies. Historically, this process was believed to occur only in endothermic vertebrates (i.e. birds and
mammals), taking place in specialized structures called germinal centers, which form in the B cell follicles of the
spleen and lymph nodes during an immune response. Here B cells mutate their immunoglobulin genes to
produce a greater diversity of receptors. The B cells then migrate within the germinal center to interact with T
follicular helper cells and follicular dendritic cells, which present intact antigen for Darwinian selection of B cell
clones. More recently, and despite an absence of germinal centers and true follicular dendritic cells, it has been
definitively shown that cold-blooded vertebrates are capable of some level of affinity maturing their antibody
responses. This finding leads to the hypothesis that a primordial B cell selection structure, or germinal center
precursor, preceded the complex stringent selection structures present in mammals.
 This project will investigate B cell selection and affinity maturation in the nurse shark, a model organism
that belongs to the oldest extant taxonomic group (Chondrichthyes) to possess B cell receptors, T cell receptors,
and major histocompatibility complex. It has previously been demonstrated that nurse sharks are capable of both
affinity maturation and immunological memory. Additionally, the nurse shark has an immunoglobulin class
consisting of only heavy chain that does not associate with light chain, IgNAR, well suited for B cell receptor
repertoire analysis. These characteristics make the nurse shark an ideal model to study the evolution of B cell
selection and affinity maturation.
 The evolution of B cell selection will be addressed through three avenues of investigation: first, the sites
of B cell selection will be identified in the nurse shark spleen, then assessed for their cellular architecture, B cell
repertoire, and cytokine transcriptome through immunofluorescent staining, laser capture microdissection, and
high throughput sequencing. Second, the nurse shark primary and affinity matured B cell repertoires will be
analyzed by sequencing and isolation of antigen-specific IgNAR clones via phage display; these will be
sequenced to evaluate clone diversity, then expressed as recombinant proteins to assess their binding affinity.
Finally, the nurse shark memory response will be characterized to determine the diversity and affinity of clones
selected for long-term immune protection and identify the signaling cytokines that maintain long-lived B cells in
sharks. The results of these aims will provide a greater understanding of the evolution of B cell selection, somatic
hypermutation, and affinity maturation.

## Key facts

- **NIH application ID:** 9976975
- **Project number:** 5F31AI147532-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Hanover Christian Matz
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,140
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976975

## Citation

> US National Institutes of Health, RePORTER application 9976975, The evolution of B cell selection and affinity maturation in ectotherms (5F31AI147532-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9976975. Licensed CC0.

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