Systematic memory B cell archiving and random display shape the human splenic marginal zone throughout life.

Area of Science:

• Immunology
• Cell Biology
• Human Aging

Background:

• Memory B cells (MBCs) are crucial for adaptive immunity.
• These cells are generated and diversified in secondary lymphoid organs.
• Understanding MBC dynamics is key to comprehending immune responses and aging.

Purpose of the Study:

• To investigate the lifespan and dynamics of human memory B cells in peripheral blood and spleen.
• To characterize the relationship between circulating, archived, and primed MBC compartments.
• To explore how these dynamics change with human aging.

Main Methods:

• Paired immunoglobulin (Ig)-gene repertoire analysis of peripheral blood (PB) and splenic MBCs.
• Analysis across different human age groups (infant, adult, elderly).
• Functional assays assessing CD21 expression on MBCs.

Main Results:

• Circulating MBCs are comprehensively archived in the spleen throughout life.
• Splenic MBC clones are preserved, uncoupled from class-switching, with increasing clonality over time.
• The splenic marginal zone (sMZ) acts as a primed MBC compartment, with CD21+ MBCs showing transient CD21high expression upon stimulation.

Conclusions:

• The human MBC system comprises three interconnected compartments: circulating, archive, and primed (sMZ).
• The dynamic interplay between these compartments shifts with age.
• These age-related changes in MBC dynamics contribute to immune aging.