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Open AccessArticle

Mining the Plasma Cell Transcriptome for Novel Cell Surface Proteins

1
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
2
Department of Medical Biology, University of Melbourne, Parkville, VIC 3010 Australia
3
CSL Limited, Parkville, VIC 3010, Australia
4
Haematology Department, Monash Health, Clayton, VIC 3168, Australia
5
Department of Clinical Haematology, Alfred Health, Melbourne 3004, Australia
6
Australian Centre for Blood Diseases, Monash University, Melbourne 3004, Australia
7
Department of Computing and Information Systems, University of Melbourne, Parkville, VIC 3010, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this study.
Int. J. Mol. Sci. 2018, 19(8), 2161; https://doi.org/10.3390/ijms19082161
Received: 28 June 2018 / Revised: 20 July 2018 / Accepted: 20 July 2018 / Published: 24 July 2018
Antibody Secreting Cells (ASCs) are a fundamental component of humoral immunity, however, deregulated or excessive antibody production contributes to the pathology of autoimmune diseases, while transformation of ASCs results in the malignancy Multiple Myeloma (MM). Despite substantial recent improvements in treating these conditions, there is as yet no widely used ASC-specific therapeutic approach, highlighting a critical need to identify novel methods of targeting normal and malignant ASCs. Surface molecules specifically expressed by the target cell population represent ideal candidates for a monoclonal antibody-based therapy. By interrogating the ASC gene signature that we previously defined we identified three surface proteins, Plpp5, Clptm1l and Itm2c, which represent potential targets for novel MM treatments. Plpp5, Clptm1l and Itm2c are highly and selectively expressed by mouse and human ASCs as well as MM cells. To investigate the function of these proteins within the humoral immune system we have generated three novel mouse strains, each carrying a loss-of-function mutation in either Plpp5, Clptm1l or Itm2c. Through analysis of these novel strains, we have shown that Plpp5, Clptm1l and Itm2c are dispensable for the development, maturation and differentiation of B-lymphocytes, and for the production of antibodies by ASCs. As adult mice lacking either protein showed no apparent disease phenotypes, it is likely that targeting these molecules on ASCs will have minimal on-target adverse effects. View Full-Text
Keywords: plasma cell; antibody; CLPTM1L; ITM2C; PLPP5; membrane protein plasma cell; antibody; CLPTM1L; ITM2C; PLPP5; membrane protein
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Trezise, S.; Karnowski, A.; Fedele, P.L.; Mithraprabhu, S.; Liao, Y.; D’Costa, K.; Kueh, A.J.; Hardy, M.P.; Owczarek, C.M.; Herold, M.J.; Spencer, A.; Shi, W.; Willis, S.N.; Nutt, S.L.; Corcoran, L.M. Mining the Plasma Cell Transcriptome for Novel Cell Surface Proteins. Int. J. Mol. Sci. 2018, 19, 2161.

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