B cells in food allergy

Approximately 10% of the world population suffers from food allergies, which usually develop allergic sensitization early in infancy to milk, egg, and peanut. In fact, some individuals with milk egg allergies seem outgrow their symptoms a few years, whereas peanut-allergic do not peanut allergy. Knowledge on immune tolerance mechanisms allergens is essential for establishing precise prevention treatments allergies.1Satitsuksanoa P. Jansen K. Globinska A. van de Veen W. Akdis M. Regulatory allergy.Front Immunol. 2018; 9: 2939Crossref PubMed Scopus (57) Google Scholar A particularly important research focus accurate quantification qualitative characterization allergen-specific memory B cells food-allergic patients tolerant individuals. Monitoring changes that occur response allergen immunotherapy may provide valuable clues about drive unresponsiveness allergens. Currently, role development allergy remains poorly understood. Here, we highlight current understanding this ‘‘Paradigms perspectives’’ article. Infants tend natural first year life. Neeland et al2Neeland M.R. Martino D.J. Dang T.D. Koplin J.J. Peters R.L. Grishin al.B-cell phenotype function infants allergy.Allergy. 2019; 74: 1022-1025Crossref (6) purified quantify circulating B-cell subsets persistent, transient healthy controls. Following Toll-like receptor 9 (CpG-2006) stimulation, produced high level IL-8 persistent group. Hence, they suggest an increase proinflammatory cytokine production lead Similarly, children age. Noh al3Noh J. Lee J.H. G. Bang S.Y. Kim H.S. Choi W.S. al.Characterisation responses IL-10-producing regulatory (Br1) cow allergy.Cell 2010; 264: 143-149Crossref (56) examined IL-10–producting cell before stimulation milk-allergic milk-tolerant subjects. IL-10 has potent immunosuppressive capacity plays major induction IgG4 suppression IgE immunotherapy. They observed Br1 were decreased group but For reason, result suggests regulated by anti-inflammatory IL-10–producing cells. Long-term vivo follow-up antigen/allergen-specific exciting area gather information clonal existence expansion specific given antigen/allergen circulation or tissues. recent study Hoh al4Hoh R.A. Joshi S.A. J.Y. Martin B.A. Varma S. Kwok al.Origins convergence gastrointestinal IgE(+) human allergy.Sci 2020; 5eaay4209Crossref (42) focusing demonstrated humans, local class switch recombination (CSR) sites contribute significantly allergen–specific antibodies.4Hoh Using high-throughput repertoire analysis, IgE-expressing and/or plasma-cell clones detected blood, stomach, duodenum, esophagus addition circulation. enriched stomach duodenum tissue, many shared similar peanut-specific sequences. It was same frequency lineages containing IgA1 IgA2 members present tract. These data CSR possibly are common events patients. This never reported mouse models, because mice cannot IgA order immunoglobulin constant heavy gene segments IgH locus. Previously, peripheral blood respiratory clone most closely related IgG1 might show sequential IgE. data, therefore, differentiation pathways who differ those allergies. addition, identified tract as reservoir IgE+ allergy, representing during oral other isotype-expressing B-lineage comparison lymphatic organs, bone marrow (Fig 1). The biological antigen-specific antibodies remain incompletely Croote al5Croote D. Darmanis Nadeau K.C. Quake S.R. High-affinity cloned single transcriptomes.Science. 362: 1306-1309Crossref (72) isolated used single-cell RNA sequencing elucidate expression splicing patterns unique these found mostly immature plasmablasts. Interestingly, showed affinity unexpected cross-reactivity different provides insight into transcriptomics enables biochemical dissection antibody class. Sensitization via skin aspect murine model epicutaneous allergens, IgG1+ preceded generation responses, suggesting determination humoral immunity could be identify at risk developing IgE-mediated allergy.6Jimenez-Saiz R. Ellenbogen Y. Koenig J.F.E. Gordon M.E. Walker Rosace al.IgG1(+) predates foods.Allergy. 165-175Crossref (27) Natural long-lasting. Santos al7Santos A.F. James L.K. Bahnson H.T. Shamji M.H. Couto-Francisco N.C. Islam al.IgG4 inhibits peanut-induced basophil mast activation peanut-tolerant sensitized allergens.J Allergy Clin 2015; 135: 1249-1256Abstract Full Text PDF (161) detectable clinically Their differences levels justify clinical compared tolerance. However, authors proposed blocking more explanation absence reactivity this, diversity there increasing somatic mutation immunotherapy, did increase.8Hoh Liu Wang C. Roskin K.M. al.Single deconvolution patients.J 2016; 137: 157-167Abstract (79) Most allergen–binding flow cytometry mutated expressed isotype-switched antibodies. results also can stimulate IgG4. between aeroallegens subjects induce Schwarz al9Schwarz Panetta V. Cappella Hofmaier Hatzler L. Rohrbach al.IgG 91 allergenic molecules childhood route exposure future sensitization: Multicentre Study birth cohort.J 138: 1426-1433.e12Abstract (35) IgG, IgG4, animal foodborne, vegetable airborne Study. IgG each higher IgE-sensitized nonsensitized age 2 7 years. prevalence relying routes exposure. Comparatively, only minor contribution children. To signatures associated life, high-dimensional mass cytometry–based profiling resting stimulated PBMCs performed versus patients.10Neeland Andorf Manohar Dunham Lyu S.C. al.Mass reveals cellular fingerprint life.Nat Commun. 11: 1091Crossref (28) findings increased frequencies activated (CD19hiHLA-DRhi), TNF-? several types including killer–cell, CD4 T-cell, monocyte-, dendritic-cell, populations, T Moreover, displayed reduced frequency, hyperresponsive naive plasmacytoid dendritic successfully validates utility power analysis interrogate interactions conclusion, common, often serious, lifelong, if outgrown years Early-age maintenance antigens crucial management Human plasma play counterregulation cells, Nevertheless, developed differently its parameters differ. uncertainty threshold persistency individual unclear. Why egg- resolve easier than peanut- shrimp-allergic individuals? What features distinctions egg-, milk-, shared? From our perspective, will key players answering remaining questions. Accordingly, further studies needed improvement novel medical future.