Premium
MS4A8B oligomerizes with CD20 (MS4A1) and modulates B cell receptor‐stimulated calcium entry
Author(s) -
Deans Julie,
Deng Lili,
Zuccolo Jonathan
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1066.10
Subject(s) - breakpoint cluster region , biology , microbiology and biotechnology , internalization , b cell receptor , cd20 , b cell , cell culture , polyclonal antibodies , receptor , antibody , immunology , genetics
The MS4A gene family comprises over 20 distinct murine and human genes expressed in hematopoeitic and other tissues. The founding member of this family, CD20 (MS4A1), is highly expressed in B lymphocytes and functions in store‐operated calcium influx activated by B cell receptor crosslinking (Li, H. et al J. Biol. Chem. (2003) 278:42427–34). Immune responses in CD20‐deficient mice appear to be normal, highlighting the possibility of compensating function from other members of the same family. In this study we examined the expression and function of a new member of the human MS4A family, MS4A8B, which was reported to be transcribed in B cell lines but not in cell lines from other hematopoeitic lineages. Using a GFP‐tagged construct expressed in the BJAB human B cell line, we found that MS4A8B co‐localised with CD20 at the plasma membrane and co‐immunoprecipitated with CD20 from detergent lysates. Like CD20, MS4A8B GFP co‐capped with the BCR in anti‐IgM stimulated cells and remained at the plasma membrane following internalization of the BCR. Over‐expression of MS4A8B in a human B cell line enhanced calcium influx following BCR stimulation. The expression of endogenous MS4A8B and its association with CD20 in primary B cells were confirmed using a new polyclonal anti‐MS4A8B antibody. Interestingly, expression of MS4A8B (but not CD20) was rapidly down‐regulated after BCR stimulation, suggesting a differential role for MS4A8B in modulating BCR‐activated calcium signalling. Funded by the Canadian Institutes of Health Research (CIHR).