Lymphocyte generation and population homeostasis throughout life

Area of Science:

• Immunology
• Gerontology
• Cell Biology

Background:

• Immune aging leads to decreased infection defense, impaired tissue repair, chronic inflammation, and autoimmunity.
• The adaptive immune system faces challenges in maintaining homeostasis due to reduced generative capacity and increased complexity.
• Thymic involution and reduced B-cell progenitor generation significantly alter immune cell populations.

Purpose of the Study:

• To elucidate the fundamental changes in T-cell and B-cell compartments during immune aging.
• To understand the functional consequences of altered immune cell composition in aged individuals.
• To identify key cellular mechanisms driving age-related immune dysfunction.

Main Methods:

• Analysis of T-cell repertoire shaping through peripheral homeostatic proliferation.
• Investigation of B-cell progenitor generation and peripheral B-cell compartment composition.
• Characterization of age-associated B cells (ABCs) and their properties.

Main Results:

• Naïve T cells function as quasi-stem cells, maintaining the T-cell compartment via peripheral proliferation and selection.
• Reduced generation of early B-cell progenitors leads to alterations in the peripheral B-cell compartment.
• A distinct, auto-inflammatory B-cell subset, age-associated B cells (ABCs), emerges with aging.

Conclusions:

• Changes in T- and B-cell composition and function are central to immune aging.
• Peripheral selection and differentiation pathways shape the aged T-cell repertoire.
• The emergence of ABCs represents a significant aspect of age-related immune dysregulation.