0000000000408747

AUTHOR

Falk Nimmerjahn

0000-0002-5418-316x

showing 4 related works from this author

Catchup: a mouse model for imaging-based tracking and modulation of neutrophil granulocytes

2015

Neutrophil granulocyte biology is a central issue of immunological research, but the lack of animal models that allow for neutrophil-selective genetic manipulation has delayed progress. By modulating the neutrophil-specific locus Ly6G with a knock-in allele expressing Cre recombinase and the fluorescent protein tdTomato, we generated a mouse model termed Catchup that exhibits strong neutrophil specificity. Transgene activity was found only in very few eosinophils and basophils and was undetectable in bone marrow precursors, including granulomonocytic progenitors (GMPs). Cre-mediated reporter-gene activation allowed for intravital two-photon microscopy of neutrophils without adoptive transfe…

MaleProgrammed cell deathGenotypeNeutrophilsTransgeneMedizinCre recombinaseMice TransgenicPeritonitisBiologyBiochemistryMiceCell MovementAnimalsAntigens LyTransgenesMolecular BiologyMice KnockoutCell DeathGene Transfer TechniquesCell BiologyCell movementMolecular biologyMice Inbred C57BLGene Expression RegulationFemaleReactive Oxygen SpeciesBiotechnologyNature Methods
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Impact of a Three Amino Acid Deletion in the CH2 Domain of Murine IgG1 on Fc-Associated Effector Functions

2008

Abstract Four murine IgG subclasses display markedly different Fc-associated effector functions because of their differential binding to three activating IgG Fc receptors (FcγRI, FcγRIII, and FcγRIV) and C1q. Previous analysis of IgG subclass switch variants of 34-3C anti-RBC monoclonal autoantibodies revealed that the IgG1 subclass, which binds only to FcγRIII and fails to activate complement, displayed the poorest pathogenic potential. This could be related to the presence of a three amino acid deletion at positions 233–235 in the CH2 domain uniquely found in this subclass. To address this question, IgG1 insertion and IgG2b deletion mutants at positions 233–235 of 34-3C anti-RBC Abs were …

Deletion mutantImmunologyAntibody AffinityDown-Regulationddc:616.07BiologySubclassProtein Structure Tertiary/geneticsMiceAnimalsImmunology and AllergyAmino AcidsEffector functionsSequence DeletionMice Knockoutchemistry.chemical_classificationMice Inbred BALB CMice Inbred NZBAnemia Hemolytic Autoimmune/genetics/immunologyReceptors IgGAutoantibodyAmino Acids/chemistry/genetics/metabolismIgg subclassesReceptors IgG/antagonists & inhibitors/genetics/metabolismPathogenicityProtein Structure TertiaryImmunoglobulin G/genetics/metabolismImmunoglobulin Switch RegionCell biologyAmino acidImmunoglobulin Heavy Chains/biosynthesis/genetics/metabolismAntibody Affinity/geneticsBiochemistrychemistryImmunoglobulin GMonoclonalMutagenesis Site-DirectedAnemia Hemolytic AutoimmuneDown-Regulation/genetics/immunologyImmunoglobulin Heavy ChainsThe Journal of Immunology
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Crucial role of aspartic acid at position 265 in the CH2 domain for murine IgG2a and IgG2b Fc-associated effector functions.

2008

Abstract Replacement of aspartic acid by alanine at position 265 (D265A) in mouse IgG1 results in a complete loss of interaction between this isotype and low-affinity IgG Fc receptors (FcγRIIB and FcγRIII). However, it has not yet been defined whether the D265A substitution could exhibit similar effects on the interaction with two other FcγR (FcγRI and FcγRIV) and on the activation of complement. To address this question, 34-3C anti-RBC IgG2a and IgG2b switch variants bearing the D265A mutation were generated, and their effector functions and in vivo pathogenicity were compared with those of the respective wild-type Abs. The introduction of the D265A mutation almost completely abolished the…

ErythrocytesAspartic Acid/genetics/physiologyAntibodies Monoclonal/toxicityImmunologyMutantReceptors Fcddc:616.07Complement Activation/genetics/immunologyAlanine/geneticsMiceStructure-Activity RelationshipProtein structureImmunoglobulin G/chemistry/metabolismProtein Isoforms/chemistry/deficiency/genetics/physiologyAspartic acidImmunology and AllergyAnimalsProtein IsoformsErythrocytes/immunologyReceptorComplement ActivationAutoantibodiesAlanineMice KnockoutAspartic AcidMice Inbred BALB CAlaninebiologyAnemia Hemolytic Autoimmune/genetics/immunologyAntibodies MonoclonalReceptors Fc/chemistry/deficiency/genetics/physiologyFragment crystallizable regionIsotypeAmino Acid Substitution/genetics/physiologySialic Acids/geneticsProtein Structure TertiaryMice Inbred C57BLBiochemistryAmino Acid SubstitutionImmunoglobulin Gbiology.proteinSialic AcidsAutoantibodies/toxicityAnemia Hemolytic AutoimmuneAntibodyProtein Structure Tertiary/genetics/physiologyJournal of immunology (Baltimore, Md. : 1950)
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Nucleoprotein-specific nonneutralizing antibodies speed up LCMV elimination independently of complement and FcγR

2013

CD8(+) T cells have an essential role in controlling lymphocytic choriomeningitis virus (LCMV) infection in mice. Here, we examined the contribution of humoral immunity, including nonneutralizing antibodies (Abs), in this infection induced by low virus inoculation doses. Mice with impaired humoral immunity readily terminated infection with the slowly replicating LCMV strain Armstrong but showed delayed virus elimination after inoculation with the faster replicating LCMV strain WE and failed to clear the rapidly replicating LCMV strain Docile, which is in contrast to the results obtained with wild-type mice. Thus, the requirement for adaptive humoral immunity to control the infection was dep…

biologyvirusesImmunologychemical and pharmacologic phenomenaLymphocytic choriomeningitismedicine.diseaseVirologyVirusNucleoproteinTiterImmunologyHumoral immunitymedicinebiology.proteinImmunology and AllergyCytotoxic T cellAntibodyCD8European Journal of Immunology
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