title: The Extracellular Domains of IgG1 and T Cell-Derived IL-4/IL-13 Are Critical for the Polyclonal Memory IgE Response In Vivo.
abstract: IgE-mediated activation of mast cells and basophils contributes to protective immunity against helminths but also causes allergic responses. The development and persistence of IgE responses are poorly understood, which is in part due to the low number of IgE-producing cells. Here, we used next generation sequencing to uncover a striking overlap between the IgE and IgG1 repertoires in helminth-infected or OVA/alum-immunized wild-type BALB/c mice. The memory IgE response after secondary infection induced a strong increase of IgE+ plasma cells in spleen and lymph nodes. In contrast, germinal center B cells did not increase during secondary infection. Unexpectedly, the memory IgE response was lost in mice where the extracellular part of IgG1 had been replaced with IgE sequences. Adoptive transfer studies revealed that IgG1+ B cells were required and sufficient to constitute the memory IgE response in recipient mice. T cell-derived IL-4/IL-13 was required for the memory IgE response but not for expansion of B cells from memory mice. Together, our results reveal a close relationship between the IgE and IgG1 repertoires in vivo and demonstrate that the memory IgE response is mainly conserved at the level of memory IgG1+ B cells. Therefore, targeting the generation and survival of allergen-specific IgG1+ B cells could lead to development of new therapeutic strategies to treat chronic allergic disorders.
authors.affiliation: Department of Infection Biology, Institute for Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Adriana
authors.initials: A
authors.lastname: Turqueti-Neves
authors.affiliation: Department of Infection Biology, Institute for Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Otte
authors.affiliation: Department of Infection Biology, Institute for Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schwartz
authors.affiliation: Department of Infection Biology, Institute for Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Michaela Erika Renate
authors.initials: ME
authors.lastname: Schmitt
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lindner
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany; Institute of Molecular Medicine, Medical Faculty, RWTH University, Aachen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Pabst
authors.affiliation: Institute for Immunology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of Infection Biology, Institute for Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen and Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Voehringer
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology / Q000637:transplantation; D049109:Cell Proliferation; D002478:Cells, Cultured; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D007156:Immunologic Memory; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009559:Nippostrongylus / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D054730:Protein Interaction Domains and Motifs; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D017206:Strongylida Infections / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology
chemical_list: D007074:Immunoglobulin G; D018793:Interleukin-13; D015847:Interleukin-4; D007073:Immunoglobulin E