Mining the Plasma Cell Transcriptome for Novel Cell Surface Proteins

• Published in: International journal of molecular sciences Vol. 19; no. 8; p. 2161
• Main Authors: Trezise, Stephanie, Karnowski, Alexander, Fedele, Pasquale L, Mithraprabhu, Sridurga, Liao, Yang, D'Costa, Kathy, Kueh, Andrew J, Hardy, Matthew P, Owczarek, Catherine M, Herold, Marco J, Spencer, Andrew, Shi, Wei, Willis, Simon N, Nutt, Stephen L, Corcoran, Lynn M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.07.2018; MDPI
• Subjects: Animals; antibody; Antibody-Producing Cells - immunology; Autoimmune diseases; B-Lymphocytes - immunology; Bone Marrow Cells - cytology; Bone Marrow Cells - immunology; Cell Line, Tumor; Cell surface; CLPTM1L; Deregulation; Gene expression; Humans; Humoral immunity; Identification methods; Immune system; Immunity, Humoral; ITM2C; Lymphocytes; Lymphocytes B; Malignancy; membrane protein; Membrane Proteins - genetics; Membrane Proteins - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Monoclonal antibodies; Multiple myeloma; Multiple Myeloma - genetics; Multiple Myeloma - immunology; Mutation; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Phenotypes; Phosphatidate Phosphatase - genetics; Phosphatidate Phosphatase - physiology; plasma cell; Plasma Cells - cytology; Plasma Cells - immunology; PLPP5; Primary Cell Culture; Proteins; Transcriptome; membrane protein; PLPP5; antibody; CLPTM1L; plasma cell; ITM2C
• DOI: 10.3390/ijms19082161
• ISSN: 1422-0067; 1661-6596

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. , and 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 , or . 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.