Mining the plasma cell transcriptome for novel cell surface proteins

Trezise, S; Karnowski, A; Fedele, PL; Mithraprabhu, S; Liao, Y; D&#39;Costa, K; Kueh, AJ; Hardy, MP; Owczarek, CM; Herold, MJ; Spencer, A; Shi, W; Willis, SN; Nutt, SL; Corcoran, LM

Author(s): Trezise, S; Karnowski, A; Fedele, PL; Mithraprabhu, S; Liao, Y; D'Costa, K; Kueh, AJ; Hardy, MP; Owczarek, CM; Herold, MJ; Spencer, A; Shi, W; Willis, SN; Nutt, SL; Corcoran, LM;
Details: Publication Year 2018-07-24,Volume 19,Issue #8,Page pii: E2161
Journal Title: International Journal of Molecular Sciences
Publication Type: Journal Article
Abstract: 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.
Publisher: MDPI
Research Division(s): Molecular Immunology; Bioinformatics; Molecular Genetics Of Cancer
PubMed ID: 30042348
Publisher's Version: https://doi.org/10.3390/ijms19082161
Open Access at Publisher's Site: https://doi.org/10.3390/ijms19082161
NHMRC Grants: NHMRC/1054925, NHMRC/1058238,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2018-08-15 03:28:55

Last Modified: 2019-01-14 12:34:35