Dataset Information

Testing the role of the Fc?RIIB immunoreceptor tyrosine-based inhibitory motif in regulation of the B cell immune response.

ABSTRACT: In vitro studies have demonstrated that the immunoreceptor tyrosine-based inhibitory motif (ITIM) of the inhibitory Fc receptor Fc?RIIB is critical for mediating attenuation of signaling via immunoreceptor tyrosine-based activation motif (ITAM) containing receptors, such as the B cell antigen receptor (BCR), when Fc?RIIB is co-cross-linked to these activation receptors. To test the role of the Fc?RIIB ITIM motif in regulation of the B cell immune response in vivo, we constructed lines of transgenic mice expressing a form of Fc?RIIB with an inactivating tyrosine (Y) to phenylalanine (F) mutation in the ITIM motif. Detailed studies of one of these lines, in which the mutant Fc?RIIB was expressed on B cells and other cell types that normally express this receptor, were performed. No quantitative differences in germinal center (GC) B cell responses were observed between the mutant Fc?RIIB transgenic line and control mice. However, serum antibody and antibody forming cell responses were often observed to be elevated in the ITIM mutant Fc?RIIB transgenic mice as compared to controls, though not to the same extent as mice deficient in expression of Fc?RIIB. Moreover, primary B cells from the ITIM mutant Fc?RIIB line did not display the same level of augmented BCR signaling as primary Fc?RIIB deficient B cells under conditions inducing co-cross-linking of Fc?RIIB and the BCR. In total, these data suggest that a functional ITIM motif is not required for all in vivo inhibitory activity of this receptor. However, we also found that the transgenic ITIM mutant Fc?RIIB receptor was expressed at abnormal levels in several hematopoietic lineages. Thus, confirmation of our findings will require the generation and analysis of mice in which an ITIM mutant form of Fc?RIIB is expressed in vivo as is the endogenous receptor.

SUBMITTER: Vuyyuru R

PROVIDER: S-EPMC4578524 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Testing the role of the FcγRIIB immunoreceptor tyrosine-based inhibitory motif in regulation of the B cell immune response.

Vuyyuru Raja R Shen Shixue S Manser Tim T

Immunity, inflammation and disease 20150604 3

In vitro studies have demonstrated that the immunoreceptor tyrosine-based inhibitory motif (ITIM) of the inhibitory Fc receptor FcγRIIB is critical for mediating attenuation of signaling via immunoreceptor tyrosine-based activation motif (ITAM) containing receptors, such as the B cell antigen receptor (BCR), when FcγRIIB is co-cross-linked to these activation receptors. To test the role of the FcγRIIB ITIM motif in regulation of the B cell immune response in vivo, we constructed lines of transge ...[more]

PMID: 26417440

Similar Datasets

Project description:The platelet surface is poorly characterized due to the low abundance of many membrane proteins and the lack of specialist tools for their investigation. In this study we identified novel human platelet and mouse megakaryocyte membrane proteins using specialist proteomics and genomics approaches. Three separate methods were used to enrich platelet surface proteins prior to identification by liquid chromatography and tandem mass spectrometry: lectin affinity chromatography, biotin/NeutrAvidin affinity chromatography, and free flow electrophoresis. Many known, abundant platelet surface transmembrane proteins and several novel proteins were identified using each receptor enrichment strategy. In total, two or more unique peptides were identified for 46, 68, and 22 surface membrane, intracellular membrane, and membrane proteins of unknown subcellular localization, respectively. The majority of these were single transmembrane proteins. To complement the proteomics studies, we analyzed the transcriptome of a highly purified preparation of mature primary mouse megakaryocytes using serial analysis of gene expression in view of the increasing importance of mutant mouse models in establishing protein function in platelets. This approach identified all of the major classes of platelet transmembrane receptors, including multitransmembrane proteins. Strikingly 17 of the 25 most megakaryocyte-specific genes (relative to 30 other serial analysis of gene expression libraries) were transmembrane proteins, illustrating the unique nature of the megakaryocyte/platelet surface. The list of novel plasma membrane proteins identified using proteomics includes the immunoglobulin superfamily member G6b, which undergoes extensive alternate splicing. Specific antibodies were used to demonstrate expression of the G6b-B isoform, which contains an immunoreceptor tyrosine-based inhibition motif. G6b-B undergoes tyrosine phosphorylation and association with the SH2 domain-containing phosphatase, SHP-1, in stimulated platelets suggesting that it may play a novel role in limiting platelet activation.

Dataset Information

Testing the role of the Fc?RIIB immunoreceptor tyrosine-based inhibitory motif in regulation of the B cell immune response.

Publications

Testing the role of the FcγRIIB immunoreceptor tyrosine-based inhibitory motif in regulation of the B cell immune response.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets