The role of Semaphorin 4C-PlexinB2 interaction in B-lymphocyte differentiation

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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.