Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - GutBCells (Cellular Dynamics of Intestinal Antibody-Mediated Immune Response)

Teaser

The role of the immune system is to clear invading pathogens and provide long lasting protection while maintaining tolerance to self-antigens. Our focus in the current ERC-StG grant studies is on the humoral arm of the immune system, and in particular, we examine how...

Summary

The role of the immune system is to clear invading pathogens and provide long lasting protection while maintaining tolerance to self-antigens. Our focus in the current ERC-StG grant studies is on the humoral arm of the immune system, and in particular, we examine how antibodies are formed and evolve over time in various tissues. Antibodies are formed by B lymphocyte that differentiate into antibody forming cells and secretes protective antibodies for a long period of time. The immune system consists of many B cells, each one carries a unique antibody with various specificity and affinity. Invading microbes activate B cells that express a specific antibody that can bind the invading pathogen and neutralize it. However, this process is not sufficient for triggering an antibody immune response and an additional signal is required for a B cell to differentiate and secrete high affinity antibodies. The goal of the study is to understand how antibody immune response provides protection against pathogens with a major focus on the intestinal tissues.

Understanding how the immune system work, can lead to the design of more efficient vaccines against infectious diseases. Furthermore, the malfunctioning of the immune system can lead to autoimmune diseases. A better understanding of how the immune system functions and how deleterious antibodies evolve can expose new checkpoints for therapeutic interventions and treatment of patients. Furthermore, defect in immune cell functions can give rise to blood cancer and lymphomas. Understanding the mechanism that control immune system changes and evolution over time may help to establish treatments for these diseases.

The objective of the current study is to understand how the antibody immune response functions. In particular, we focus on a less explored immune site, the gut tissues. We examined how do high affinity antibodies evolve over time and aim to uncover new checkpoints in this process.

Work performed

We have discovered a new molecule that cell-cell interactions and regulates the antibody immune response.
We designed a new technique for analysis of immune cell niches without knowing which cells reside in the niche.
We described the chain of events that underlie protective antibody immune response in the intestinal tissues.

Final results

We continue to examine immune cell interaction in the intestinal immune response. We examine the contribution of helper T cells to antibody affinity maturation in gut lymph nodes.
Using new techniques that involve whole organ imaging we examine multiple immune cell niches and compare their dynamics and cellular compositions.
By using new IgA reporter mice, we study class switch recombination to IgA in the gut.
We further explore the routs takes by cells for egressing different niches in gut tissues.
In all of these studies, we examine the role of the microbiome and how the immune response control the commensal bacteria in the gut.