Research

B cell, Antibody, and Virus

RESEARCH GOAL

Our laboratory is dedicated to uncovering the fundamental mechanisms driving immune responses against a broad range of antigenically diverse viruses, such as influenza and SARS-CoV-2, with a particular focus on B cells—crucial players in adaptive immunity responsible for producing pathogen-specific antibodies. B cells exhibit a unique capacity for continuous evolution, acquiring mutations in their antibody-encoding genes, which enhances the diversity and affinity of antibodies, thus effectively countering viruses that evade immune defenses. Our research seeks to understand the evolutionary dynamics of B cell responses to both vaccination and infection, examining how B cells adapt, the mutations that enhance their efficacy, and the conditions that foster optimal antibody production. Through this work, we aim to contribute valuable insights that could guide the development of next-generation vaccines and therapies, ultimately improving strategies to protect against infectious diseases.

Background

Q. Why we need to study B cell response in HUMAN?

A. Pre-existing immunity should be considered for understanding immune response.

Animal models lack prior exposure to antigens, while our bodies have encountered a diverse range of antigens, resulting in the formation of pre-existing immunity including memory B cells (MBCs) and bone marrow plasma cells (BMPCs). Interestingly, the immune system prefers to recall pre-existing immune cells rather than to stimulate de novo response. This indicates that pre-existing immune cells participate in immune response to subsequent variant viral infections. Therefore, studying the human immune system can provide valuable insights to understand how pre-existing immunity shapes subsequent antibody responses.

Aim 1. Understanding Co-evolution of Virus and Immunity: Arms Race

Our bodies repeatedly encounter diverse pathogens and receive multiple rounds of immunization, leading to the formation of memory B cells. However, viruses constantly mutate their genome to evade the memory immune response. In response to newly emerging viruses, B cell immunity also continuously evolves via somatic hypermutation, thereby enhancing antibody functionality. This dynamic interplay between viruses and B cells drives the co-evolutionary process. Here, our study aims to understand the evolutionary trajectory of B cell immune response: 1) identifying and characterizing B cells generated in response to re-emerging or variant virus infections and 2) evaluating the changes in antibody responses to immune-escaping mutations on viral protein?

Aim 2. Understanding Long-term Persisting Immunity

Q. How to induce durable immune memory lasting for a lifetime?

The longevity of vaccine efficacy is highly variable, with some vaccines conferring life-long protection, while others providing only short-term protection. In other words, not all vaccines elicit the same B cell responses, and this is referred to as the heterogeneity of vaccine-induced B cell response. The durability of vaccine-induced immunity is determined by several factors including vaccine types, environmental factors, and genetics. Our research mainly is focused on the impact of B cell-intrinsic factors on vaccine durability. By investigating the B cell-intrinsic factors that contribute to vaccine durability, such as gene expression patterns and genetic variations, we can gain insights into how to improve vaccine efficacy and develop more durable vaccines.

APPROACH

Classical Immunolgical Method