Activated P13Kd disrupts germinal centre GC T(fh)/GC B cell cross talk and B cell antibody coding

Research output: Contribution to journalArticle

Abstract

In a study by Priete and research groups from the USA and Italy,1 amouse model with a mutation in the P13K gene that causes theactivation of the P13K pathway was used to demonstrate thecellular and molecular mechanisms underlying the main biologicaland clinical features of the rare human immunodeficiency diseaseknown as APDS or activated P13kδ syndrome. In humans, theoveractivation of the P13Kδ pathway causes recurrent respiratoryinfections with secondary bronchiectasis, lymphopenia, lymphoproliferation,and poor vaccination responses.2 The P13Kδ mousemodel has a gain-of-function (GOF) mutation in the P13Kδ geneand shows lymphopenia, lymphoproliferation, and poor responsesto vaccination, similar to the findings in human disease. Thesefindings suggested that the P13Kδ-GOF mouse could be a usefultool to dissect the cellular and molecular mechanisms andpathways that contribute to the similar human disease. Theauthors then probed the immune response/s in the P13Kδ GOFmouse model using a variety of challenges and methods toidentify where and how the P13Kδ-GOF-activated gene disturbsthe cellular and molecular pathways of competent antibodyformation and used comparisons with wild-type (WT) mice andnormal human donors to help define the APDS phenotype andQ1Q23 the P13Kδ-GOF mutant mouse model (MM).
Original languageEnglish
Pages (from-to)1-3
JournalCellular and Molecular Immunology
DOIs
Publication statusPublished - 08 Oct 2019

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Germinal Center
B-Lymphocytes
Antibodies
Lymphopenia
Vaccination
Mutation
Bronchiectasis
Italy
Genes
Phenotype
Research

Keywords

  • P13Kd gene, immunodeficiency, antibody coding, microbiome

Cite this

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title = "Activated P13Kd disrupts germinal centre GC T(fh)/GC B cell cross talk and B cell antibody coding",
abstract = "In a study by Priete and research groups from the USA and Italy,1 amouse model with a mutation in the P13K gene that causes theactivation of the P13K pathway was used to demonstrate thecellular and molecular mechanisms underlying the main biologicaland clinical features of the rare human immunodeficiency diseaseknown as APDS or activated P13kδ syndrome. In humans, theoveractivation of the P13Kδ pathway causes recurrent respiratoryinfections with secondary bronchiectasis, lymphopenia, lymphoproliferation,and poor vaccination responses.2 The P13Kδ mousemodel has a gain-of-function (GOF) mutation in the P13Kδ geneand shows lymphopenia, lymphoproliferation, and poor responsesto vaccination, similar to the findings in human disease. Thesefindings suggested that the P13Kδ-GOF mouse could be a usefultool to dissect the cellular and molecular mechanisms andpathways that contribute to the similar human disease. Theauthors then probed the immune response/s in the P13Kδ GOFmouse model using a variety of challenges and methods toidentify where and how the P13Kδ-GOF-activated gene disturbsthe cellular and molecular pathways of competent antibodyformation and used comparisons with wild-type (WT) mice andnormal human donors to help define the APDS phenotype andQ1Q23 the P13Kδ-GOF mutant mouse model (MM).",
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AB - In a study by Priete and research groups from the USA and Italy,1 amouse model with a mutation in the P13K gene that causes theactivation of the P13K pathway was used to demonstrate thecellular and molecular mechanisms underlying the main biologicaland clinical features of the rare human immunodeficiency diseaseknown as APDS or activated P13kδ syndrome. In humans, theoveractivation of the P13Kδ pathway causes recurrent respiratoryinfections with secondary bronchiectasis, lymphopenia, lymphoproliferation,and poor vaccination responses.2 The P13Kδ mousemodel has a gain-of-function (GOF) mutation in the P13Kδ geneand shows lymphopenia, lymphoproliferation, and poor responsesto vaccination, similar to the findings in human disease. Thesefindings suggested that the P13Kδ-GOF mouse could be a usefultool to dissect the cellular and molecular mechanisms andpathways that contribute to the similar human disease. Theauthors then probed the immune response/s in the P13Kδ GOFmouse model using a variety of challenges and methods toidentify where and how the P13Kδ-GOF-activated gene disturbsthe cellular and molecular pathways of competent antibodyformation and used comparisons with wild-type (WT) mice andnormal human donors to help define the APDS phenotype andQ1Q23 the P13Kδ-GOF mutant mouse model (MM).

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