B-cell receptor physical properties affect relative IgG1 and IgE responses in mouse egg allergy
Mutated and unmutated IgE and IgG play different and partly opposing roles in allergy development, but the mechanisms controlling their relative production are incompletely understood. Here, we analyzed the IgE-response in murine food allergy. Deep sequencing of the complementary-determining region...
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| Veröffentlicht in: | Mucosal immunology 2022-06, Vol.15 (6), p.1375-1388 |
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| creator | Udoye, Christopher C. Rau, Christina N. Freye, Sarah M. Almeida, Larissa N. Vera-Cruz, Sarah Othmer, Kai Korkmaz, Rabia Ü. Clauder, Ann-Katrin Lindemann, Timo Niebuhr, Markus Ott, Fabian Kalies, Kathrin Recke, Andreas Busch, Hauke Fähnrich, Anke Finkelman, Fred D. Manz, Rudolf A. |
| description | Mutated and unmutated IgE and IgG play different and partly opposing roles in allergy development, but the mechanisms controlling their relative production are incompletely understood. Here, we analyzed the IgE-response in murine food allergy. Deep sequencing of the complementary-determining region (CDR) repertoires indicated that an ongoing unmutated extrafollicular IgE response coexists with a germinal center response, even after long-lasting allergen challenges. Despite overall IgG1-dominance, a significant proportion of clonotypes contained several-fold more IgE than IgG1. Clonotypes with differential bias to either IgE or IgG1 showed distinct hypermutation and clonal expansion. Hypermutation rates were associated with different physiochemical binding properties of individual B-cell receptors (BCR). Increasing BCR signaling strength inhibited class switching from IgG1 to IgE in vitro, preferentially constraining IgE formation. These data indicate that antigen-binding properties of individual BCRs determine differential IgE hypermutation and IgE versus IgG1 production on the level of single B-cell clones. |
| doi_str_mv | 10.1038/s41385-022-00567-y |
| format | Article |
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Here, we analyzed the IgE-response in murine food allergy. Deep sequencing of the complementary-determining region (CDR) repertoires indicated that an ongoing unmutated extrafollicular IgE response coexists with a germinal center response, even after long-lasting allergen challenges. Despite overall IgG1-dominance, a significant proportion of clonotypes contained several-fold more IgE than IgG1. Clonotypes with differential bias to either IgE or IgG1 showed distinct hypermutation and clonal expansion. Hypermutation rates were associated with different physiochemical binding properties of individual B-cell receptors (BCR). Increasing BCR signaling strength inhibited class switching from IgG1 to IgE in vitro, preferentially constraining IgE formation. These data indicate that antigen-binding properties of individual BCRs determine differential IgE hypermutation and IgE versus IgG1 production on the level of single B-cell clones.</description><identifier>ISSN: 1933-0219</identifier><identifier>EISSN: 1935-3456</identifier><identifier>DOI: 10.1038/s41385-022-00567-y</identifier><identifier>PMID: 36114245</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Allergens ; Allergology ; Anaphylaxis ; Animals ; Antibodies ; Antigens ; B-cell receptor ; B-Lymphocytes ; Biomedical and Life Sciences ; Biomedicine ; Class switching ; Cloning ; Dermatology ; Diarrhea ; Egg Hypersensitivity - metabolism ; Food allergies ; Gastroenterology ; Immunoglobulin E ; Immunoglobulin E - metabolism ; Immunoglobulin G ; Immunoglobulin G - metabolism ; Immunology ; Lymphocytes B ; Medical research ; Mice ; Physical properties ; Plasma ; Receptor mechanisms ; Receptors, Antigen, B-Cell - genetics ; Roles</subject><ispartof>Mucosal immunology, 2022-06, Vol.15 (6), p.1375-1388</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><rights>The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-b7d0f910a5b6fc192ca4e5a29d055f290a9d6089f09038f185630b8c8f23f9f03</citedby><cites>FETCH-LOGICAL-c474t-b7d0f910a5b6fc192ca4e5a29d055f290a9d6089f09038f185630b8c8f23f9f03</cites><orcidid>0000-0003-1263-7693</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2740753236?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,776,780,881,27903,27904,64361,64363,64365,72215</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36114245$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Udoye, Christopher C.</creatorcontrib><creatorcontrib>Rau, Christina N.</creatorcontrib><creatorcontrib>Freye, Sarah M.</creatorcontrib><creatorcontrib>Almeida, Larissa N.</creatorcontrib><creatorcontrib>Vera-Cruz, Sarah</creatorcontrib><creatorcontrib>Othmer, Kai</creatorcontrib><creatorcontrib>Korkmaz, Rabia Ü.</creatorcontrib><creatorcontrib>Clauder, Ann-Katrin</creatorcontrib><creatorcontrib>Lindemann, Timo</creatorcontrib><creatorcontrib>Niebuhr, Markus</creatorcontrib><creatorcontrib>Ott, Fabian</creatorcontrib><creatorcontrib>Kalies, Kathrin</creatorcontrib><creatorcontrib>Recke, Andreas</creatorcontrib><creatorcontrib>Busch, Hauke</creatorcontrib><creatorcontrib>Fähnrich, Anke</creatorcontrib><creatorcontrib>Finkelman, Fred D.</creatorcontrib><creatorcontrib>Manz, Rudolf A.</creatorcontrib><title>B-cell receptor physical properties affect relative IgG1 and IgE responses in mouse egg allergy</title><title>Mucosal immunology</title><addtitle>Mucosal Immunol</addtitle><addtitle>Mucosal Immunol</addtitle><description>Mutated and unmutated IgE and IgG play different and partly opposing roles in allergy development, but the mechanisms controlling their relative production are incompletely understood. Here, we analyzed the IgE-response in murine food allergy. Deep sequencing of the complementary-determining region (CDR) repertoires indicated that an ongoing unmutated extrafollicular IgE response coexists with a germinal center response, even after long-lasting allergen challenges. Despite overall IgG1-dominance, a significant proportion of clonotypes contained several-fold more IgE than IgG1. Clonotypes with differential bias to either IgE or IgG1 showed distinct hypermutation and clonal expansion. Hypermutation rates were associated with different physiochemical binding properties of individual B-cell receptors (BCR). Increasing BCR signaling strength inhibited class switching from IgG1 to IgE in vitro, preferentially constraining IgE formation. These data indicate that antigen-binding properties of individual BCRs determine differential IgE hypermutation and IgE versus IgG1 production on the level of single B-cell clones.</description><subject>Allergens</subject><subject>Allergology</subject><subject>Anaphylaxis</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>B-cell receptor</subject><subject>B-Lymphocytes</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Class switching</subject><subject>Cloning</subject><subject>Dermatology</subject><subject>Diarrhea</subject><subject>Egg Hypersensitivity - metabolism</subject><subject>Food allergies</subject><subject>Gastroenterology</subject><subject>Immunoglobulin E</subject><subject>Immunoglobulin E - metabolism</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - metabolism</subject><subject>Immunology</subject><subject>Lymphocytes B</subject><subject>Medical research</subject><subject>Mice</subject><subject>Physical properties</subject><subject>Plasma</subject><subject>Receptor mechanisms</subject><subject>Receptors, Antigen, B-Cell - 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Here, we analyzed the IgE-response in murine food allergy. Deep sequencing of the complementary-determining region (CDR) repertoires indicated that an ongoing unmutated extrafollicular IgE response coexists with a germinal center response, even after long-lasting allergen challenges. Despite overall IgG1-dominance, a significant proportion of clonotypes contained several-fold more IgE than IgG1. Clonotypes with differential bias to either IgE or IgG1 showed distinct hypermutation and clonal expansion. Hypermutation rates were associated with different physiochemical binding properties of individual B-cell receptors (BCR). Increasing BCR signaling strength inhibited class switching from IgG1 to IgE in vitro, preferentially constraining IgE formation. 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| subjects | Allergens Allergology Anaphylaxis Animals Antibodies Antigens B-cell receptor B-Lymphocytes Biomedical and Life Sciences Biomedicine Class switching Cloning Dermatology Diarrhea Egg Hypersensitivity - metabolism Food allergies Gastroenterology Immunoglobulin E Immunoglobulin E - metabolism Immunoglobulin G Immunoglobulin G - metabolism Immunology Lymphocytes B Medical research Mice Physical properties Plasma Receptor mechanisms Receptors, Antigen, B-Cell - genetics Roles |
| title | B-cell receptor physical properties affect relative IgG1 and IgE responses in mouse egg allergy |
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