Allergen Drives Class Switching to IgE in the Nasal Mucosa in Allergic Rhinitis
Open accessAbstract
IgE-expressing B cells are over 1000 times more frequent in the nasal B cell than the peripheral blood B cell population. We have investigated the provenance of these B cells in the nasal mucosa in allergic rhinitis. It is generally accepted that expression of activation-induced cytidine deaminase and class switch recombination (CSR) occur in lymphoid tissue, implying that IgE-committed B cells must migrate through the circulation to the nasal mucosa. Our detection of mRNA for activation-induced cytidine, multiple germline gene transcripts, and ε circle transcripts in the nasal mucosa of allergic, in contrast to nonallergic control subjects, however, indicates that local CSR occurs in allergic rhinitis. The germline gene transcripts and ε circle transcripts in grass pollen-allergic subjects are up-regulated during the season and also when biopsies from allergic subjects are incubated with the allergen ex vivo. These results demonstrate that allergen stimulates local CSR to IgE, revealing a potential target for topical therapies in allergic rhinitis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The respiratory airway mucosa is a site of IgE production during allergic inflammation, as demonstrated in AR and LAR, with somatic hypermutation and class switching occurring in the nasal mucosa.
“The respiratory airway mucosa is a site of IgE production during allergic inflammation, as has been demonstrated in patients with AR309-312 and LAR,299-301,303-307 with both somatic hypermutation and class switching occurring in the nasal mucosa.309,312-315”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [312]
The Discussion reports direct evidence of local class switching to IgE in the nasal mucosa of patients with allergic rhinitis and states that IgE is synthesized there. It discusses somatic hypermutation as generally accompanying class switching and cites a separate study of local hypermutation, but does not itself demonstrate that process in the nasal mucosa. The paper addresses allergic rhinitis, not LAR; the citing sentence assigns LAR to a separate group of citations. (LLM, conf=0.83)
Experimental — accuracy not yet measuredAllergic rhinitis patients have specific IgE in the nasal mucosa, with evidence that class switching and antibody production occur locally.
“In addition to positive systemic sIgE, AR patients have been shown to have sIgE in the nasal mucosa with evidence that class switching and antibody production occurs locally.309-312,377,950,951”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [312]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
Muramatsu, M., Kinoshita, K., Fagarasan, S., Yamada, S., Shinkai, Y., & Honjo, T. (2000) · Cell · doi:10.1016/s0092-8674(00)00078-7 · Cited by 3,475 · see citing works
Muramatsu, M., Sankaranand, V. S., Anant, S., Sugai, M., Kinoshita, K., Davidson, N. O., & Honjo, T. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.26.18470 · Cited by 1,165 · see citing works
(1957) · Journal of the American Pharmaceutical Association (Scientific ed ) · doi:10.1002/jps.3030460129 · Cited by 710 · see citing works
Immunoglobulin class switching
Stavnezer, J. (1996) · Current Opinion in Immunology · doi:10.1016/s0952-7915(96)80058-6 · Cited by 452 · see citing works
Jabara, H. H., Fu, S. M., Geha, R. S., & Vercelli, D. (1990) · The Journal of Experimental Medicine · doi:10.1084/jem.172.6.1861 · Cited by 444 · see citing works
In situ class switching and differentiation to IgA-producing cells in the gut lamina propria
Fagarasan, S., Kinoshita, K., Muramatsu, M., Ikuta, K., & Honjo, T. (2001) · Nature · doi:10.1038/35098100 · Cited by 430 · see citing works
Yssel, H., de Vries, J. E., Koken, M. H. M., BLITTERSWIJK, W. J. V., & Spits, H. (1984) · Journal of Immunological Methods · doi:10.1016/0022-1759(84)90450-2 · Cited by 373 · see citing works
Humbert, M. J. C., Menz, G., Sun, Y., Corrigan, C. J., Robinson, D. S., Durham, S. R., & Kay, A. B. (1999) · Immunology Today · doi:10.1016/s0167-5699(99)01535-2 · Cited by 340 · see citing works
Self-citationPawankar, R., Okuda, M., Yssel, H., Okumura, K., & Ra, C. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119311 · Cited by 340 · see citing works
Stott, D. I., Hiepe, F., Hummel, M., Steinhauser, G., & Berek, C. (1998) · Journal of Clinical Investigation · doi:10.1172/jci3234 · Cited by 334 · see citing works
Ludewig, B., Odermatt, B., LeibundGut‐Landmann, S., Hengartner, H., & Zinkernagel, R. M. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.8.1493 · Cited by 309 · see citing works
Kitaura, J., Song, J., Tsai, M. M., Asai, K., Maeda‐Yamamoto, M., Mócsai, A., Kawakami, Y., Liu, F., Lowell, C. A., Barisas, B. G., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1735525100 · Cited by 261 · see citing works
The AID enzyme induces class switch recombination in fibroblasts
Okazaki, I., Kinoshita, K., Muramatsu, M., Yoshikawa, K., & Honjo, T. (2002) · Nature · doi:10.1038/nature727 · Cited by 260 · see citing works
Gray, D. (1993) · Annual Review of Immunology · doi:10.1146/annurev.immunol.11.1.49 · Cited by 255 · see citing works
Structure of human immunoglobulin gamma genes: implications for evolution of a gene family
Takahashi, N., Ueda, S., Obata, M., et al. (1982) · Cell · doi:10.1016/0092-8674(82)90183-0 · Cited by 228 · see citing works
Zhang, K., Clark, E. A., & Saxon, A. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.6.1836 · Cited by 220 · see citing works
Kim, H. J., Krenn, V., Steinhauser, G., & Berek, C. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.5.3053 · Cited by 218 · see citing works
Molecular Processes that Regulate Class Switching
Stavnezer, J. (2000) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-59641-4_6 · Cited by 202 · see citing works
KleinJan, A., Vinke, J. G., Severijnen, L. W. F. M., & Fokkens, W. J. (2000) · European Respiratory Journal · doi:10.1034/j.1399-3003.2000.15.11.x · Cited by 181 · see citing works
Ying, S., Humbert, M. J. C., Meng, Q., Pfister, R., Menz, G., Gould, H. J., Kay, A. B., & Durham, S. R. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.114339 · Cited by 175 · see citing works
Self-citationFujieda, S., Díaz-Sánchez, D., & Saxon, A. (1998) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.19.3.3143 · Cited by 174 · see citing works
Durham, S. R., Gould, H. J., Thienes, C. P., Jacobson, M. R., Masuyama, K., Rak, S., Lowhagen, O., Schotman, E., Cameron, L., & Hamid, Q. A. (1997) · European Journal of Immunology · doi:10.1002/eji.1830271123 · Cited by 168 · see citing works
Self-citationKinoshita, K., Harigai, M., Fagarasan, S., Muramatsu, M., & Honjo, T. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.221454398 · Cited by 165 · see citing works
Coker, H. A., Durham, S. R., & Gould, H. J. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.10.5602 · Cited by 149 · see citing works
Self-citationFujieda, S., Zhang, K., & Saxon, A. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.5.2318 · Cited by 133 · see citing works
Randen, I., Brown, D., Thompson, K. M., et al. (1992) · The Journal of Immunology · doi:10.4049/jimmunol.148.10.3296 · Cited by 125 · see citing works
Cameron, L., GOUNNI, A. S., Frenkiel, S., Lavigne, F., Vercelli, D., & Hamid, Q. A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.7.3816 · Cited by 121 · see citing works
Cameron, L., Hamid, Q., Wright, E., Nakamura, Y., Christodoulopoulos, P., Muro, S., Frenkiel, S., Lavigne, F., Durham, S., & Gould, H. (2000) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2000.107398 · Cited by 107 · see citing works
Self-citationZhang, K., Mills, F. C., & Saxon, A. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.152.7.3427 · Cited by 90 · see citing works
Cameron, L. A., Durham, S. R., Jacobson, M. R., Masuyama, K., Júlíusson, S., Gould, H. J., Lowhagen, O., Minshall, E. M., & Hamid, Q. A. (1998) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(98)70244-1 · Cited by 87 · see citing works
Self-citationZhou, C. J., Saxon, A., & Zhang, K. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.4.1887 · Cited by 82 · see citing works
A biopsy method to obtain high quality specimens of nasal mucosa.
Fokkens, W. J., Feltkamp‐Vroom, T. M., Gerritsma, & Rijntjes, E. (1988) · PubMed · Cited by 78 · see citing works
Human Ig S γ regions and their participation in sequential switching to IgE
Mills, F. C., Mitchell, M., Harindranath, N., et al. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.6.3021 · Cited by 77 · see citing works
Cerutti, A., Zan, H., Kim, E. C., Shah, S., Schattner, E. J., Schaffer, A., & Casali, P. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.11.6594 · Cited by 73 · see citing works
Snow, R. E., Djukanović, R., & Stevenson, F. K. (1999) · Immunology · doi:10.1046/j.1365-2567.1999.00910.x · Cited by 61 · see citing works
Fear, D. J., McCloskey, N., O'Connor, B. J., et al. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.7.4529 · Cited by 46 · see citing works
Self-citationVoswinkel, J., Weisgerber, K., Pfreundschuh, M., et al. (2001) · Arthritis Research & Therapy · doi:10.1186/ar297 · Cited by 39 · see citing works
Rheumatoid factor isotype switch and somatic mutation variants within rheumatoid arthritis synovium
Williams, Moyes, & Mageed (1999) · Immunology · doi:10.1046/j.1365-2567.1999.00841.x · Cited by 26 · see citing works
Krenn, V., König, A., Hensel, F., et al. (1999) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1999.00767.x · Cited by 24 · see citing works
Enumeration of IgE secreting B cells
King, C. L., Thyphronitis, G., & Nutman, T. B. (1990) · Journal of Immunological Methods · doi:10.1016/0022-1759(90)90395-c · Cited by 24 · see citing works
Fundamentals of Immunology: 4th edn
Tiffin, A. I. (1968) · PubMed Central · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Allergic Rhinitis and its Impact on Asthma (ARIA) 2008*
Bousquet, J., Khaltaev, N., Cruz, A. A., Denburg, J., Fokkens, W. J., Togias, A., Zuberbier, T., Baena‐Cagnani, C. E., Canonica, G. W., Van Weel, C., et al. (2008) · Allergy · doi:10.1111/j.1398-9995.2007.01620.x · Cited by 4,729 · see citing works
Self-citationAllergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 Revision
Brożek, J. L., Bousquet, J., Baena-Cagnani, C. E., Bonini, S., Canonica, G. W., Casale, T. B., van Wijk, R. G., Ohta, K., Zuberbier, T., & Schünemann, H. J. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.06.047 · Cited by 1,813 · see citing works
International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis
Wise, S. K., Lin, S. Y., Toskala, E., Orlandi, R. R., Akdis, C. A., Alt, J. A., Azar, A., Baroody, F. M., Bachert, C., Canonica, G. W., et al. (2018) · International Forum of Allergy & Rhinology · doi:10.1002/alr.22073 · Cited by 557 · see citing works
Eifan, A. O., & Durham, S. R. (2016) · Clinical & Experimental Allergy · doi:10.1111/cea.12780 · Cited by 379 · see citing works
Self-citationThe who, where, and when of IgE in allergic airway disease
Dullaers, M., De Bruyne, R., Ramadani, F., Gould, H. J., Gevaert, P., & Lambrecht, B. N. (2012) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.10.029 · Cited by 194 · see citing works
Self-citationRondón, C., Doña, I., López, S., Campo, P., Romero, J. J., Torres, M. J., Mayorga, C., & Blanca, M. (2008) · Allergy · doi:10.1111/j.1398-9995.2008.01695.x · Cited by 166 · see citing works
Klunker, S., Saggar, L. R., Seyfert-Margolis, V., Asare, A. L., Casale, T. B., Durham, S. R., & Francis, J. N. (2007) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2007.05.034 · Cited by 129 · see citing works
Self-citationLocal IgE in non‐allergic rhinitis
Campo, P., Rondón, C., Gould, H. J., Barrionuevo, E., Gevaert, P., & Blanca, M. (2015) · Clinical & Experimental Allergy · doi:10.1111/cea.12476 · Cited by 101 · see citing works
Self-citationPowe, D. G., Groot Kormelink, T., Sisson, M., Blokhuis, B. J., Kramer, M. F., Jones, N. S., & Redegeld, F. A. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.07.025 · Cited by 87 · see citing works
Nonallergic rhinitis and lower airway disease
Rondón, C., Bogas, G., Barrionuevo, E., Blanca, M., Torres, M. J., & Campo, P. (2017) · Allergy · doi:10.1111/all.12988 · Cited by 74 · see citing works
Campo, P., Salas, M., Blanca-López, N., & Rondón, C. (2016) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2015.12.008 · Cited by 59 · see citing works
Local mucosal immunoglobulin E production: does allergy exist in non‐allergic rhinitis?
Powe, D. G., & Jones, N. S. (2006) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2006.02593.x · Cited by 31 · see citing works
James, L. K., & Durham, S. R. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.09.029 · Cited by 12 · see citing works
Self-citation
- Authors
- Takhar, P., Smurthwaite, L., Coker, H. A., Fear, D. J., Banfield, G. K., Carr, V. A., Durham, S. R., & Gould, H. J.
- Affiliations
- King's College London (GB)
- Imperial College London (GB)
- Corresponding author
- Takhar, Pooja
- Smurthwaite, Lyn
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-04
- Volume
- 174
- Issue
- 8
- Pages
- 5024-5032
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1731104758
- Cited by
- 230
- References
- 43
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 11 · 2020: 10 · 2019: 10 · 2018: 11 · 2017: 11 · 2016: 20 · 2015: 16 · 2014: 14 · 2013: 7 · 2012: 9
- FWCI
- 8.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- British Lung Foundation
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- allergic rhinitis, class switch recombination, IgE, nasal mucosa, B cells, activation-induced cytidine deaminase, germline transcripts, grass pollen allergy, allergen stimulation, topical treatment
- MeSH terms
- AICDA (Activation-Induced Cytidine Deaminase), Adult, Allergens, B-Lymphocytes, Base Sequence, Cytidine Deaminase, Female, Rhinitis, Allergic, Seasonal, Humans, Immunoglobulin E, Male, Middle Aged, Molecular Sequence Data, Nasal Mucosa, Rhinitis, Allergic, Perennial, RNA, Messenger, Sequence Homology, Nucleic Acid, Case-Control Studies, Immunoglobulin Class Switching, DNA, Complementary, Cytosine Deaminase, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review