Open AccessSystematic memory B cell archiving and random display shape the human splenic marginal zone throughout life
Author(s) -
Artur Kibler,
Bettina Budeus,
Ekaterina Homp,
Kevin Bronischewski,
Victoria Berg,
Ludger Sellmann,
Florian Murke,
Andreas Heinold,
Falko M. Heinemann,
Monika Lindemann,
Isabelle BekeredjianDing,
Peter A. Horn,
Carsten J. Kirschning,
Ralf Küppers,
Marc Seifert
Publication year - 2021
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20201952
Subject(s) - marginal zone , spleen , biology , immunology , immune system , immunological memory , lymphatic system , antibody , compartment (ship) , repertoire , memory b cell , memory cell , b cell , microbiology and biotechnology , immunity , oceanography , physics , transistor , quantum mechanics , voltage , acoustics , geology
Human memory B cells (MBCs) are generated and diversified in secondary lymphoid tissues throughout the organism. A paired immunoglobulin (Ig)-gene repertoire analysis of peripheral blood (PB) and splenic MBCs from infant, adult, and elderly humans revealed that throughout life, circulating MBCs are comprehensively archived in the spleen. Archive MBC clones are systematically preserved and uncoupled from class-switching. Clonality in the spleen increases steadily, but boosts at midlife, thereby outcompeting small clones. The splenic marginal zone (sMZ) represents a primed MBC compartment, generated from a stochastic exchange within the archive memory pool. This is supported by functional assays, showing that PB and splenic CD21+ MBCs acquire transient CD21high expression upon NOTCH2-stimulation. Our study provides insight that the human MBC system in PB and spleen is composed of three interwoven compartments: the dynamic relationship of circulating, archive, and its subset of primed (sMZ) memory changes with age, thereby contributing to immune aging.