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Allergen-specific immunoglobulin E (IgE) antibodies mediate pathology in diseases such as allergic rhinitis and food allergy. Memory B cells (MBCs) contribute to circulating IgE by regenerating IgE-producing plasma cells upon allergen encounter. Here, we report a population of type 2-polarized MBCs defined as CD23, IL-4Rα, and CD32 at both the transcriptional and surface protein levels. These MBC2s are enriched in IgG1- and IgG4-expressing cells while constitutively expressing germline transcripts for IgE. Allergen-specific B cells from patients with allergic rhinitis and food allergy were enriched in MBC2s. Furthermore, MBC2s generated allergen-specific IgE during sublingual immunotherapy, thereby identifying these cells as a major reservoir for IgE. The identification of MBC2s provides insights into the maintenance of IgE memory, which is detrimental in allergic diseases but could be beneficial in protection against venoms and helminths.
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http://dx.doi.org/10.1126/scitranslmed.adi0944 | DOI Listing |
Curr Opin Immunol
December 2024
Jaffe Food Allergy Institute, Division of Allergy and Immunology, Department of Pediatrics, and Lipschultz Precision Immunology Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:
Immunoglobulin E (IgE)-mediated allergic diseases are driven by high-affinity allergen-specific IgE antibodies. IgE antibodies bind to Fc epsilon receptors on mast cells, prompting their degranulation and initiating inflammatory reactions upon allergen crosslinking. While most IgE-producing plasma cells have short lifespans, and IgE memory B cells are exceedingly rare, studies have indicated that non-IgE-expressing type 2-polarized IgG memory B cells serve as a reservoir of IgE memory in allergies.
View Article and Find Full Text PDFOrg Biomol Chem
August 2024
University Center Varaždin, University North, HR-42000 Varaždin, Croatia.
Muramyl dipeptide (MDP) is the smallest essential peptidoglycan substructure capable of promoting both innate and adaptive immune responses. Herein, we report on the design, synthesis, and study of the adjuvant properties of two novel MDP analogs containing an achiral adamantyl moiety attached to the desmuramyl dipeptide (DMP) pharmacophore and additionally modified by one mannosyl subunit (derivative 7) or two mannosyl subunits (derivative 11). Mannose substructures were introduced in order to assess how the degree of mannosylation affects the immune response and nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) binding affinity, compared to the reference compound ManAdDMP.
View Article and Find Full Text PDFSci Immunol
March 2024
Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA. Email:
Type 2-polarized memory B cells sustain food allergy and allergic rhinitis by rapidly differentiating into pathogenic IgE-producing plasma cells.
View Article and Find Full Text PDFSci Transl Med
February 2024
ALK-Abelló A/S, 2970 Hørsholm, Denmark.
Allergen-specific immunoglobulin E (IgE) antibodies mediate pathology in diseases such as allergic rhinitis and food allergy. Memory B cells (MBCs) contribute to circulating IgE by regenerating IgE-producing plasma cells upon allergen encounter. Here, we report a population of type 2-polarized MBCs defined as CD23, IL-4Rα, and CD32 at both the transcriptional and surface protein levels.
View Article and Find Full Text PDFJ Invest Dermatol
May 2024
Department of Dermatology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Electronic address:
Cutaneous T-cell lymphomas are a heterogeneous group of neoplasms originating in the skin, with mycosis fungoides (MF) and Sézary syndrome (SS) representing the most common variants. The cellular origin of cutaneous lymphomas has remained controversial owing to their immense phenotypic heterogeneity that obfuscates lineage reconstruction on the basis of classical surface biomarkers. To overcome this heterogeneity and reconstruct the differentiation trajectory of malignant cells in MF and SS, TCR sequencing was performed in parallel with targeted transcriptomics at the single-cell resolution among cutaneous samples in MF and SS.
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