Reference number : GC-2017-Q1-03461, amendment number : , agreement type : G, recipient legal name : Mazer, Bruce (McGill University)|Mazer, Bruce (Université McGill), recipient country : CA, recipient province : nan, recipient city : Quebec|Québec, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : B-lymphocytes are the cells that make antibodies, provide assistance to T-cells to help magnify immune responses against microbes and other foreign invaders, and produce chemicals called cytokines which transfer information from one cell to another. To improve the ability of B-lymphocytes to communicate, when B-cells are activated, important molecules on B-cells are brought to a pole on one side of the cell, in a structure known as the immune synapse. The molecules that control the formation of these synapses are not well studied. It is important to understand the regulation of the immune synapse to understand how cells communicate and potentially improve problems such as autoimmunity and antibody deficiencies. My laboratory discovered that a molecule known as Semaphorin 4C, thought to be only important in the nervous system, is produced when B-cells are activated to mature or to respond to particular types of foreign proteins. The full function of this molecule in B-cells is not known. However, our data suggests that Semaphorin 4C acts a part of the anchor allowing B-cells to properly form immune synapses. In mice that do not have this molecule, B-cells which are activated do not form normal immune synapses and their B-cells do not make normal amounts of antibodies or cytokines. 
 
Semaphorin 4C is known to interact with molecules such as F-actin, that work together to allow a cell to change shape, much like pulling the strings on a marionette. This project will examine how Semaphorin 4C interacts within the cell skeleton to assist in forming an immune synapse, and determine the consequences of the signals within B-cells when the immune synapse is poorly formed. Understanding the role of this anchor molecule will help to understand fundamental aspects of the biology of the cells that form antibodies, and help us potentially better understand diseases such as immune deficiencies, allergies and autoimmune conditions., program purpose french : B-lymphocytes are the cells that make antibodies, provide assistance to T-cells to help magnify immune responses against microbes and other foreign invaders, and produce chemicals called cytokines which transfer information from one cell to another. To improve the ability of B-lymphocytes to communicate, when B-cells are activated, important molecules on B-cells are brought to a pole on one side of the cell, in a structure known as the immune synapse. The molecules that control the formation of these synapses are not well studied. It is important to understand the regulation of the immune synapse to understand how cells communicate and potentially improve problems such as autoimmunity and antibody deficiencies. My laboratory discovered that a molecule known as Semaphorin 4C, thought to be only important in the nervous system, is produced when B-cells are activated to mature or to respond to particular types of foreign proteins. The full function of this molecule in B-cells is not known. However, our data suggests that Semaphorin 4C acts a part of the anchor allowing B-cells to properly form immune synapses. In mice that do not have this molecule, B-cells which are activated do not form normal immune synapses and their B-cells do not make normal amounts of antibodies or cytokines. 
 
Semaphorin 4C is known to interact with molecules such as F-actin, that work together to allow a cell to change shape, much like pulling the strings on a marionette. This project will examine how Semaphorin 4C interacts within the cell skeleton to assist in forming an immune synapse, and determine the consequences of the signals within B-cells when the immune synapse is poorly formed. Understanding the role of this anchor molecule will help to understand fundamental aspects of the biology of the cells that form antibodies, and help us potentially better understand diseases such as immune deficiencies, allergies and autoimmune conditions., agreement title english : The role of Semaphorin 4C-PlexinB2 interaction in B-lymphocyte differentiation, agreement title french : The role of Semaphorin 4C-PlexinB2 interaction in B-lymphocyte differentiation, agreement number : RGPIN, agreement value : 130000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada