CD19 regulates ADAM28‐mediated Notch2 cleavage to control the differentiation of marginal zone precursors to MZ B cells

As the first line of defence, marginal zone (MZ) B cells play principal roles in clearing blood‐borne pathogens during infection and are over‐primed in autoimmune diseases. However, the basic mechanisms underlying MZ B‐cell development are still unclear. We found here that CD19 deficiency blocked the differentiation of marginal zone precursors (MZP) to MZ B cells, whereas CD19 expression in CD19‐deficient MZP rescues MZ B‐cell generation. Furthermore, CD19 regulates Notch2 cleavage by up‐regulating ADAM28 expression in MZP. Finally, we found that CD19 suppressed Foxo1 expression to promote ADAM28 expression in MZP. These results suggest that CD19 controls the differentiation of MZP to MZ B cells by regulating ADAM28‐mediated Notch2 cleavage. Thus, we demonstrated the basic mechanisms underlying the differentiation of MZP to MZ B cells.     

The splenic marginal zone in humans and rodents: an enigmatic compartment and its inhabitants

The role of the spleen in B memory cell development and maintenance is attracting increased attention. Studies in mice and rats have indicated that memory functions are associated with large B cells residing in the marginal zone (MZ) of the spleen. Although the cellular composition of the MZ is relatively well known in these species, controversies exist about the function of MZ B cells, their dependence on the presence of the spleen and the stage at which their development branches from that of recirculating follicular B cells. Additional confusion has arisen with respect to MZ B cells in humans, because the microscopic anatomy of the human splenic MZ differs decisively from that of rodents. Several recent publications indicate that the functional and migratory properties of human MZ B cells may be species-specific. The hypothesis derived from these publications and from our immunohistological observations implies that at least a major number of human splenic CD27⁺ MZ B cells are migratory. Phenotypic data suggest a recirculation pathway between the spleen and mucosal tissues in humans.     

Interplay between CXCR4 and CCR2 regulates bone marrow exit of dendritic cell progenitors

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Epistatic genetic interactions between Insm1 and Ikzf2 during cochlear outer hair cell development

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Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine

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STAT3 signaling in B cells controls germinal center zone organization and recycling

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Organized B cell sites in cartilaginous fishes reveal the evolutionary foundation of germinal centers

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DRAK2 contributes to type 1 diabetes by negatively regulating IL-2 sensitivity to alter regulatory T cell development

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Stem cell-based modeling and single-cell multiomics reveal gene-regulatory mechanisms underlying human skeletal development

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Prevalent and immunodominant CD8 T cell epitopes are conserved in SARS-CoV-2 variants

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Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations

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Tumor-specific CD4 T cells instruct monocyte fate in pancreatic ductal adenocarcinoma

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FoxM1 coordinates cell division,protein synthesis,and mitochondrial activity in a subset of β cells during acute metabolic stress

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Variant enterovirus A71 found in immune-suppressed patient binds to heparan sulfate and exhibits neurotropism in B-cell-depleted mice

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Dynamic interplay between IL-1 and WNT pathways in regulating dermal adipocyte lineage cells during skin development and wound regeneration

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Psoriatic and rheumatoid arthritis joints differ in the composition of CD8+ tissue-resident memory T cell subsets

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Elevated FBXW10 drives hepatocellular carcinoma tumorigenesis via AR-VRK2 phosphorylation-dependent GAPDH ubiquitination in male transgenic mice

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