AUTHOR=Zuccolo Jonathan , Deng Lili , Unruh Tammy , Sanyal Ratna , Bau Jeremy A., Storek Jan , Demetrick Douglas J., Luider Joanne M., Auer-Grzesiak Iwona , Mansoor Adnan , Deans Julie P.

TITLE=Expression of MS4A and TMEM176 Genes in Human B Lymphocytes

JOURNAL=Frontiers in Immunology

VOLUME=4

YEAR=2013

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2013.00195

DOI=10.3389/fimmu.2013.00195

ISSN=1664-3224

ABSTRACT=<p>The <italic>MS4A</italic> gene family in humans includes <italic>CD20</italic> and at least 15 other genes. CD20 exists as homo-oligomers in the plasma membrane, however different MS4A proteins expressed in the same cell may hetero-oligomerize. Given the importance of CD20 in B-cell function and as a therapeutic target, we sought to explore the potential for CD20 hetero-oligomerization with other MS4A proteins. We investigated expression in primary human B-cells of the four <italic>MS4A</italic> genes previously shown to be expressed in human B-cell lines (<italic>MS4A4A</italic>, <italic>MS4A6A</italic>, <italic>MS4A7</italic>, <italic>MS4A8B</italic>), as well as two genes comprising the closely related <italic>TMEM176</italic> gene family, with a view to identifying candidates for future investigation at the protein level. <italic>TMEM176A</italic> and <italic>TMEM176B</italic> transcripts were either not detected, or were detected at relatively low levels in a minority of donor B-cell samples. <italic>MS4A4A</italic> and <italic>MS4A8B</italic> transcripts were not detected in any normal B-cell sample. <italic>MS4A6A</italic> and <italic>MS4A7</italic> transcripts were detected at low levels in most samples, however the corresponding proteins were not at the plasma membrane when expressed as GFP conjugates in BJAB cells. We also examined expression of these genes in chronic lymphocytic leukemia (CLL), and found that it was similar to normal B-cells with two exceptions. First, whereas <italic>MS4A4A</italic> expression was undetected in normal B-cells, it was expressed in 1/14 CLL samples. Second, compared to expression levels in normal B-cells, <italic>MS4A6A</italic> transcripts were elevated in 4/14 CLL samples. In summary, none of the <italic>MS4A/TMEM176</italic> genes tested was expressed at high levels in normal or in most CLL B-cells. <italic>MS4A6A</italic> and <italic>MS4A7</italic> were expressed at low levels in most B-cell samples, however the corresponding proteins may not be positioned at the plasma membrane. Altogether, these data suggest that CD20 normally does not form hetero-oligomers with other MS4A proteins and that there are unlikely to be other MS4A proteins in CLL that might provide useful alternate therapeutic targets.</p>