Spatial Dynamics of Intestinal B Cell Immunoreceptor Signaling in Health and Disease (IBD)

Using single-molecule imaging to visualize B cell receptor signaling across gut compartments, this project uncovers how intestinal B cell education breaks down in IBD, revealing new targets for therapeutic intervention.
Complete Crohn's Disease Gastrointestinal Diseases Ulcerative Colitis Adaptive Immunity Animal Models B Cell Biology Biological & Mechanistic Cytokine Signaling Experimental Platforms & Models Immune Profiling Immune Tolerance Microbiome–Immune Interactions Single Cell Technologies Spatial Biology Therapeutic Development Translational & Clinical

Funding Year: 2023

Project Overview

The immune system must carefully balance defending against infections while tolerating the body's own tissues and beneficial gut bacteria — a balance that breaks down in inflammatory bowel disease (IBD). B cells, which produce antibodies, are key players in this process, but how they are trained in the gut and how that training goes wrong in disease is poorly understood. This project applies advanced imaging technology to study B cell immunoreceptor signaling in both healthy and inflamed intestinal tissue, comparing mouse models of IBD with steady-state conditions. By mapping how B cells behave across different gut compartments — including mesenteric lymph nodes, Peyer's patches, and the lamina propria — the study aims to identify the mechanisms by which intestinal B cells become pathogenic and contribute to chronic inflammation.

Impact & Innovation

Mapping the immune missteps behind gut disease.

 

Using single-molecule imaging, this project revealed that B cell antigen handling differs across gut compartments and that chronic inflammation drives germinal center expansion throughout the intestine.

  • Closed a significant knowledge gap in how intestinal B cell signaling differs across gut compartments and breaks down in IBD
  • Revealed differential B cell antigen handling and germinal center expansion during colitis — findings that catalyzed a V Foundation Scholar Award and a pending NIH DP2
  • Advances the Consortium’s Shared Mechanisms Across Autoimmune Diseases pillar, with an imaging platform applicable across autoimmune disease research
Research Approach

A framework designed for discovery

This project combined custom-built high-content imaging with mouse models of intestinal inflammation to study B cell immunoreceptor signaling dynamics in health and disease. The work moved from platform development and single-molecule visualization through comparative analysis of healthy and IBD-like conditions.

Custom-built imaging platform enabling single-molecule resolution visualization of antigen internalization and B cell receptor signaling; image analysis using Halo software to quantify antigen uptake across B cell populations; DSS-induced colitis mouse models; and use of the Confetti allele to track germinal center dynamics in vivo. 


Mouse models of IBD (DSS-induced colitis) and steady-state intestinal tissue, B cell populations isolated from mesenteric lymph nodes, Peyer’s patches, and lamina propria, and single-molecule imaging datasets quantifying antigen internalization and germinal center structure across disease states.

Characterization of how intestinal B cell education and immunoreceptor signaling differ across gut compartments and break down during chronic inflammation, with the goal of identifying therapeutic targets that modulate BCR signaling or antibody class switching in IBD. Findings are designed to extend to human studies and inform broader autoimmune disease research.

Investigators & Institutions

Powering the science

Principal Investigator

Carla R. Nowosad, PhD, Colton Consortium Member

Assistant Professor, Department of Pathology, NYU Grossman School of Medicine / NYU Langone Health

Colton Centers & Institutions

Judith & Stewart Colton Center for Autoimmunity at NYU Langone Health

NYU Grossman School of Medicine

Research Outputs

From insight to impact

  • V Foundation V Scholar Award: $600,000 (Carla Nowosad, 2025–2027). 
  • NIH DP2 Award: $1,500,000 (Carla Nowosad, 2025–2030) [Pending Council approval, score 23].