title: Polyclonal hyper-IgE mouse model reveals mechanistic insights into antibody class switch recombination.
abstract: Preceding antibody constant regions are switch (S) regions varying in length and repeat density that are targets of activation-induced cytidine deaminase. We asked how participating S regions influence each other to orchestrate rearrangements at the IgH locus by engineering mice in which the weakest S region, Sε, is replaced with prominent recombination hotspot Sμ. These mice produce copious polyclonal IgE upon challenge, providing a platform to study IgE biology and therapeutic interventions. The insertion enhances ε germ-line transcript levels, shows a preference for direct vs. sequential switching, and reduces intraswitch recombination events at native Sμ. These results suggest that the sufficiency of Sμ to mediate IgH rearrangements may be influenced by context-dependent cues.
authors.affiliation: Genentech, Inc., South San Francisco, CA 94080.
authors.forename: Shahram
authors.initials: S
authors.lastname: Misaghi
authors.forename: Kate
authors.initials: K
authors.lastname: Senger
authors.forename: Tao
authors.initials: T
authors.lastname: Sai
authors.forename: Yan
authors.initials: Y
authors.lastname: Qu
authors.forename: Yonglian
authors.initials: Y
authors.lastname: Sun
authors.forename: Kajal
authors.initials: K
authors.lastname: Hamidzadeh
authors.forename: Allen
authors.initials: A
authors.lastname: Nguyen
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Jin
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zhou
authors.forename: Donghong
authors.initials: D
authors.lastname: Yan
authors.forename: Wei Yu
authors.initials: WY
authors.lastname: Lin
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Lin
authors.forename: Maria N
authors.initials: MN
authors.lastname: Lorenzo
authors.forename: Andrew
authors.initials: A
authors.lastname: Sebrell
authors.forename: Jiabing
authors.initials: J
authors.lastname: Ding
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Patrick
authors.initials: P
authors.lastname: Caplazi
authors.forename: Cary D
authors.initials: CD
authors.lastname: Austin
authors.forename: Mercedesz
authors.initials: M
authors.lastname: Balazs
authors.forename: Merone
authors.initials: M
authors.lastname: Roose-Girma
authors.forename: Laura
authors.initials: L
authors.lastname: DeForge
authors.forename: Søren
authors.initials: S
authors.lastname: Warming
authors.forename: Wyne P
authors.initials: WP
authors.lastname: Lee
authors.forename: Vishva M
authors.initials: VM
authors.lastname: Dixit
authors.forename: Ali A
authors.initials: AA
authors.lastname: Zarrin
mesh_terms: D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D055879:Gene Knock-In Techniques; D018390:Gene Targeting; D056426:Genetic Loci / Q000235:genetics; D005854:Germ Cells / Q000378:metabolism; D006825:Hybridomas; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007073:Immunoglobulin E / Q000378:metabolism*; D007139:Immunoglobulin epsilon-Chains / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D023421:Models, Animal; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic
chemical_list: D007139:Immunoglobulin epsilon-Chains; D007148:Immunoglobulin mu-Chains; D012333:RNA, Messenger; D007073:Immunoglobulin E
keywords: AICDA; allergy; asthma; germline transcription; immunoglobulin
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