Obtaining a molecular understanding of antibody secretion

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Constitutive secretion is the process by which cells deliver newly made protein to their outside. Cells can secrete a variety of different proteins and the most biologically and clinically important ones include collagen, cytokines and antibodies. Constitutive secretion is key to both normal heath and wellbeing as well as the manufacture of certain medicines such as therapeutic antibodies. Surprisingly, our understanding of this important process remains poor. This lack of basic knowledge will not only hinder improvements in the manufacturing of new drugs but also the development of novel medicines for the treatment of secretory-based diseases. My laboratory is interested in discovering the cellular machinery required for secretion. We are identifying this machinery by comparing cells which have high levels of secretion to those which do not using a technique called mass-spectrometry which allows the abundance of proteins to be measured. Our hypothesis is that cells which are actively involved in secretion should have more of the machinery required for performing this process. The cells we are comparing for these studies are B-cells and plasma cells. Plasma cells are the antibody producing cells of the immune system and they are capable of making and secreting hundreds of millions of antibodies per day while B-cells do not secrete any antibodies. Our pilot studies have identified several new factors which we believe are involved in secretion so indicating that a more comprehensive study is warranted. Once we have identified this novel secretory machinery will then work out how these proteins function by removing them from plasma cells using a technique called RNAi and determining whether the cells can still secrete antibodies. The knowledge generated from our research will benefit society because it will increase our understanding of a fundamental cellular process and in the future may help in the development of new manufacturing processes for therapeutic antibody production, tests for diagnosing disease and developing novel medicines for targeting diseases caused by inappropriate secretion.