BACKGROUND: Humoral immunocompetence develops stepwise throughout life and contributes to individual susceptibility to infection, immunodeficiency, autoimmunity, and neoplasia. Immunoglobulin heavy chain (IgH) isotype serum levels can partly explain such age-related differences, but their relationship with the IgH isotype distribution within memory B-cell (MBC) and plasma cell (PCs) compartments remains to be investigated. OBJECTIVE: We studied the age-related distribution of MBCs and PCs expressing different IgH isotypes in addition to the immature/transitional and naive B-cell compartments. METHODS: B-cell and PC subsets and plasma IgH isotype levels were studied in cord blood (n = 19) and peripheral blood (n = 215) from healthy donors aged 0 to 90 years by using flow cytometry and nephelometry, respectively. RESULTS: IgH-switched MBCs expressing IgG1, IgG2, IgG3, IgA1, and IgA2 were already detected in cord blood and newborns at very low counts, whereas CD27+IgM++IgD+ MBCs only became detectable at 1 to 5 months and remained stable until 2 to 4 years, and IgD MBCs peaked at 2 to 4 years, with both populations decreasing thereafter. MBCs expressing IgH isotypes of the second immunoglobulin heavy chain constant region (IGHC) gene block (IgG1, IgG3, and IgA1) peaked later during childhood (2-4 years), whereas MBCs expressing third IGHC gene block immunoglobulin isotypes (IgG2, IgG4, and IgA2) reached maximum values during adulthood. PCs were already detected in newborns, increasing in number until 6 to 11 months for IgM, IgG1, IgG2, IgG3, IgA1, and IgA2; until 2 to 4 years for IgD; and until 5 to 9 years for IgG4 and decreasing thereafter. For most IgH isotypes (except IgD and IgG4), maximum plasma levels were reached after PC and MBC counts peaked. CONCLUSIONS: PC counts reach maximum values early in life, followed by MBC counts and plasma IgH isotypes. Importantly, IgH isotypes from different IGHC gene blocks show different patterns, probably reflecting consecutive cycles of IgH isotype switch recombination through life.
- Klíčová slova
- IgH isotype, Immunoglobulins, age-related values, flow cytometry, memory B cells, normal B cells, plasma cells, reference ranges, subclass,
- MeSH
- B-lymfocyty imunologie MeSH
- dítě MeSH
- dospělí MeSH
- humorální imunita imunologie MeSH
- imunoglobulinové izotypy krev imunologie MeSH
- imunologická paměť imunologie MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- novorozenec MeSH
- plazmatické buňky imunologie MeSH
- předškolní dítě MeSH
- přesmyk imunoglobulinových tříd imunologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stárnutí imunologie MeSH
- těžké řetězce imunoglobulinů imunologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- imunoglobulinové izotypy MeSH
- těžké řetězce imunoglobulinů MeSH
Tick-induced allergy to red meat is associated with anti-α-Gal IgE antibody levels. We propose that tick salivary prostaglandin E2 triggers antibody class switching in mature B cells, increasing the levels of anti-α-Gal IgE antibodies. Immune tolerance to α-Gal in blood type B individuals might reduce the risk to this allergy.
- Klíčová slova
- PGE(2), blood groups, food allergy, immunology, tick, α-Gal,
- MeSH
- alfa-galaktosidasa imunologie MeSH
- červené maso * MeSH
- dinoproston imunologie MeSH
- imunoglobulin E imunologie MeSH
- klíšťata imunologie MeSH
- kousnutí klíštětem komplikace imunologie MeSH
- lidé MeSH
- potravinová alergie etiologie imunologie MeSH
- přesmyk imunoglobulinových tříd imunologie MeSH
- sliny imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alfa-galaktosidasa MeSH
- dinoproston MeSH
- imunoglobulin E MeSH
BACKGROUND: Mutations in PIK3CD and PIK3R1 cause activated PI3K-δ syndrome (APDS) by dysregulation of the PI3K-AKT pathway. METHODS: We studied precursor and peripheral B-cell differentiation and apoptosis via flowcytometry. Furthermore, we performed AKT-phosphorylation assays and somatic hypermutations (SHM) and class switch recombination (CSR) analysis. RESULTS: We identified 13 patients of whom 3 had new mutations in PIK3CD or PIK3R1. Patients had low total B-cell numbers with increased frequencies of transitional B cells and plasmablasts, while the precursor B-cell compartment in bone marrow was relatively normal. Basal AKT phosphorylation was increased in lymphocytes from APDS patients and natural effector B cells where most affected. PI3K mutations resulted in altered SHM and CSR and increased apoptosis. CONCLUSIONS: The B-cell compartment in APDS patients is affected by the mutations in PI3K. There is reduced differentiation beyond the transitional stage, increased AKT phosphorylation and increased apoptosis. This B-cell phenotype contributes to the clinical phenotype.
- Klíčová slova
- APDS, Apoptosis, B cells, B-cell differentiation, PI3Kδ,
- MeSH
- agamaglobulinemie genetika imunologie MeSH
- aktivace lymfocytů genetika imunologie MeSH
- B-lymfocyty imunologie MeSH
- buněčná diferenciace genetika imunologie MeSH
- dítě MeSH
- dospělí MeSH
- fosfatidylinositol-3-kinasy třídy I genetika MeSH
- fosfatidylinositol-3-kinasy třídy Ia MeSH
- fosfatidylinositol-3-kinasy genetika MeSH
- fosforylace genetika MeSH
- infekce genetika MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace genetika imunologie MeSH
- plazmatické buňky imunologie MeSH
- předškolní dítě MeSH
- prekurzorové B-lymfoidní buňky imunologie MeSH
- přesmyk imunoglobulinových tříd genetika imunologie MeSH
- protoonkogenní proteiny c-akt genetika MeSH
- recidiva MeSH
- signální transdukce genetika MeSH
- somatická hypermutace imunoglobulinových genů genetika imunologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fosfatidylinositol-3-kinasy třídy I MeSH
- fosfatidylinositol-3-kinasy třídy Ia MeSH
- PIK3CD protein, human MeSH Prohlížeč
- PIK3R1 protein, human MeSH Prohlížeč
- protoonkogenní proteiny c-akt MeSH
