# Characterization of Lamprey B cells and Antibodies

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $615,243

## Abstract

PROJECT SUMMARY
As one of two lineages of extant jawless vertebrates, lampreys represent a pivotal branch of vertebrate
phylogeny; they offer a critical source of information for understanding the evolutionary origins of our adaptive
immune system. While immunoglobulin domain-based receptors mediate adaptive immunity in all jawed
vertebrate groups, the variable lymphocyte receptor (VLR) system in lampreys and hagfishes is based on
receptors constructed of leucine-rich repeats (LRR). The VLRs are assembled by a gene conversion-like process
that sequentially copies sequences donated by fragmentary LRR cassettes into an incomplete germline VLR
gene. Although structurally unrelated to immunoglobulin and T-cell receptors, the function of three types of VLRs
are nonetheless rooted in B- (VLRB) and T-like lymphocytes (VLRA and VLRC), indicating that the basic genetic
programs for these cell types are a fundamental feature of adaptive immunity in all vertebrates. The proposed
studies focus on the diversity, functions and translational application of the lamprey VLRB antibodies, which are
expressed in a cell-surface form on B-like lymphocytes and as secreted polymeric antibody by mature plasma
cells. Our first aim is to characterize the development of the VLRB system beginning with early feeding larvae
and thereafter in multiple tissues of three-to-four-year larvae and adults. CRISPR/Cas9 strategies will be used
to perturb the function of candidate B-like cell regulators and signal mediators in embryos and larvae. We will
characterize the developing VLRB repertoire by analyzing high fidelity long-read sequence data for each
lymphopoietic tissue and developmental stage. We will also analyze scRNA-seq data from early larva and
ammocoete tissues to identify and characterize subsets of B-like cells and their stages in differentiation. In aim
two we will characterize the composite VLRB receptor. VLRB is expressed as a GPI-linked protein on the surface
of lamprey B-like cells, therefore implying that antigen-induced signaling requires associated transmembrane
domain proteins with cytoplasmic signaling capacity. We will conduct pull down assays on extracts from lamprey
VLRB lymphocytes using VLRB specific monoclonal antibodies and use mass spectrometry to identify
coprecipitated proteins. This analysis will be guided and supplemented by a set of candidate signal mediators
that we have identified from VLRB cell transcriptomes and scRNA-seq datasets generated in these studies. In
aim three we will produce and characterize monoclonal lamprey VLRB antibodies for basic and translational
applications. The analysis is focused on VLRB antibodies against highly lethal brain (glioblastoma and
astrocytoma) and ovarian tumors.

## Key facts

- **NIH application ID:** 10804062
- **Project number:** 2R01AI072435-17A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Max Dale Cooper
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $615,243
- **Award type:** 2
- **Project period:** 2007-01-15 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10804062

## Citation

> US National Institutes of Health, RePORTER application 10804062, Characterization of Lamprey B cells and Antibodies (2R01AI072435-17A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10804062. Licensed CC0.

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