Identification of a human splenic marginal zone B cell precursor with NOTCH2-dependent differentiation properties

2014/04/14 by Marc Descatoire, Sandra Weller, Sabine Irtan +19 · 26 citations
Immunology and Microbiology · #T-cell and B-cell Immunology #Immune Cell Function and Interaction #Immunotherapy and Immune Responses

paper · pdf · doi:10.1084/jem.20132203

Abstract

Mouse splenic marginal zone precursors (MZPs) differentiate into marginal zone B (MZB) cells under a signaling pathway involving Notch2 and its ligand, delta-like 1 ligand (Dll1). We report the identification of an MZP subset in the spleen of young children. These MZPs differentiate into MZ-like B cells in vitro in the presence of OP9 cells expressing human DLL1, as demonstrated by the up-regulation of classical MZB cell markers. A set of diagnostic genes discriminating IgM+IgD+CD27+ blood and splenic MZB cells from switched B cells was identified (up-regulation of SOX7, down-regulation of TOX, COCH, and HOPX), and their expression during the induction assay mirrored the one of MZB cells. Moreover, Alagille patients with a NOTCH2 haploinsufficiency display a marked reduction of IgM+IgD+CD27+ B cells in blood, whereas their switched memory B cells are not affected. Altogether, these results argue in favor of the existence of a rodent-like MZB cell lineage in humans.

Cited by

• Invariant natural killer T cells balance B cell immunity
• Genome-Wide Analysis Uncovers Novel Recurrent Alterations in Primary Central Nervous System Lymphomas. [europepmc]
• Apoptotic cell responses in the splenic marginal zone: a paradigm for immunologic reactions to apoptotic antigens with implications for autoimmunity. [europepmc]
• Checkpoints for Autoreactive B Cells in the Peripheral Blood of Lupus Patients Assessed by Flow Cytometry. [europepmc]
• mTOR intersects antibody-inducing signals from TACI in marginal zone B cells. [europepmc]
• Spatiotemporal segregation of human marginal zone and memory B cell populations in lymphoid tissue. [europepmc]
• Molecular regulation of peripheral B cells and their progeny in immunity. [europepmc]
• AIRE expression controls the peripheral selection of autoreactive B cells. [europepmc]
• Induction of metabolic quiescence defines the transitional to follicular B cell switch. [europepmc]
• Challenges and Opportunities for Consistent Classification of Human B Cell and Plasma Cell Populations. [europepmc]
• Differential Expression of IgM and IgD Discriminates Two Subpopulations of Human Circulating IgM + IgD + CD27 + B Cells That Differ Phenotypically, Functionally, and Genetically. [europepmc]
• Molecular Aspects and Future Perspectives of Cytokine-Based Anti-cancer Immunotherapy. [europepmc]
• Comprehensive analyses of B-cell compartments across the human body reveal novel subsets and a gut-resident memory phenotype. [europepmc]
• Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells. [europepmc]
• Human marginal zone B cell development from early T2 progenitors. [europepmc]
• Relevance of Notch Signaling for Bone Metabolism and Regeneration. [europepmc]
• Notch Signaling in B Cell Immune Responses. [europepmc]
• Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets. [europepmc]
• B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease. [europepmc]
• Resting innate-like B cells leverage sustained Notch2/mTORC1 signaling to achieve rapid and mitosis-independent plasma cell differentiation. [europepmc]
• Notch signaling pathway: architecture, disease, and therapeutics. [europepmc]
• Dynamic spectrum of ectopic lymphoid B cell activation and hypermutation in the RA synovium characterized by NR4A nuclear receptor expression. [europepmc]
• Multi-omics blood atlas reveals unique features of immune and platelet responses to SARS-CoV-2 Omicron breakthrough infection. [europepmc]
• NF-kB's contribution to B cell fate decisions. [europepmc]
• CD23 + IgG1 + memory B cells are poised to switch to pathogenic IgE production in food allergy. [europepmc]
• The chromatin landscape of pathogenic transcriptional cell states in rheumatoid arthritis. [europepmc]

Related

• MARGINAL ZONE B CELLS
• Early Notch signals from fibroblastic reticular cells program effector CD8+ T cell differentiation
• Immunoarchitecture of Distinct Reticular Fibroblastic Domains in the White Pulp of Mouse Spleen
• The biology of marginal zone lymphoma subtypes: challenge and relevance of classification
• Follicular helper- and peripheral helper-like T cells drive autoimmune disease in human immune system mice