2021
DOI: 10.1084/jem.20201952 View full text |Buy / Rent full text
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Abstract: 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 sma… Show more

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“…Our own data support that infant B-cell subsets differ substantially in their gene expression profiles from adult B cells: human ontogenetically early B cells provide accelerated but transient immune responses and are IGHV gene-unmutated (11). Throughout life, the accumulation, homeostatic expansion, and recirculation of IGHV gene-mutated B cells shape the sMZ B-cell pool (8). Notably, homing of memory B cells (MBCs) to the sMZ enhances at approximately 2 years and reaches an adult level at approximately 5 years of age, which coincides with efficient protection from infections with encapsulated bacteria (5,12).…”
Section: Introductionsupporting
“…The human spleen is considered immunologically immature at below 2 years (6, 7); although sMZ B cells are principally detectable (8), they have been described as antigen naïve B cells (NBCs) based on the lack of CD27 expression (7). Previous studies on human sMZ B-cell development suggest that unique diversification mechanisms (9,10) and distinct sMZ B-cell precursors (3) exist in infants.…”
Section: Introductionmentioning
“…MZL B cells in humans, and MZ cells in hypoxic mice, also recover more slowly than other B cell subsets. The reasons for this are unknown, but human MZ B cells appear to be derived from T2 transitional B cells and/or memory B cells (Kibler et al, 2021;Tull et al, 2021), both of which are profoundly depleted in COVID--19. This alone may hamper recovery, but additional unknown factors may also determine reconstitution.…”
Section: Discussionmentioning
“…The elephant at issue, the marginal zone B cell (MZB), does not fall neatly into innate or adaptive compartments but displays elements of both. Here, we highlight two papers on human MZB development and memory (Tull et al, 2021;Kibler et al, 2021), which look at both ends of the beast. By applying single-cell RNA sequencing (RNA-seq), flow spectrometry, and antibody gene mutational analysis techniques, these studies provide a higher-resolution view of these enigmatic compartments.…”
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“…Meanwhile, naturalist Kibler and colleagues (Kibler et al, 2021) evaluated changes in the human splenic B cell compartment with age, comparing the B cell receptor diversity and clonal abundance of peripheral blood and splenic memory B cells from the same donors. 141 individuals of various ages were assessed by flow cytometry for the composition of the splenic and peripheral blood B cell compartments.…”
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