Intestinal newborn regulatory B cell antibodies modulate microbiota communities

Area of Science:

• Immunology
• Microbiology
• Developmental Biology

Background:

• The function of immunoglobulins from IL-10-producing regulatory B cells is not well understood.
• Regulatory B cells play a critical role in immune system development and homeostasis.

Purpose of the Study:

• To investigate the role of a specific newborn regulatory B cell population (nBreg) in early life immunity and microbiome establishment.
• To characterize the immunoglobulin repertoire and function of nBregs.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) to identify nBreg signature and distribution in fetal and neonatal tissues.
• Cloning and characterization of monoclonal antibodies from intestinal nBregs.
• Analysis of antibody reactivity against early microbiota and their impact on microbial communities.

Main Results:

• Identified a novel newborn regulatory B cell population (nBreg) that suppresses immunoglobulin M (IgM) production via IL-10.
• Newborn germline-encoded antibodies from nBregs show reactivity against diverse early gut bacteria.
• nBreg-derived antibodies modulate microbial community diversity and function, partly through energy metabolism.

Conclusions:

• nBreg populations are crucial for facilitating early-life microbiome establishment.
• These findings shed light on the complex, seemingly paradoxical roles of regulatory B cells in early development.