CS1 (CRACC) induces Proliferation and Autocrine Cytokine expression on Activated human B Lymphocytes (86.3)

Abstract

Abstract CS1 (CRACC, CD319), a member of the CD2 family of cell surface receptors is implicated in the activation of NK cell- mediated cytotoxicity. Previous studies showed that CS1 is also expressed on activated B cells. However, the functional role of CS1 in human B-lymphocytes is not known. Two isoforms of CS1, CS1-L and CS1-S are expressed in human NK cells that differentially regulate NK cell function. CS1-L contains immunoreceptor tyrosine-based switch motifs (ITSMs) in its cytoplasmic domain whereas CS1-S lacks ITSM. Here we show that human B lymphocytes express only CS1-L isoform and its expression is upregulated upon B cell activation with various stimulators. Moreover, anti-CS1 mAb strongly enhanced proliferation of both freshly isolated as well as activated B cells. The enhanced proliferation effects of CS1 were most prominent on B cells activated by anti-CD40 mAbs and/or hrIL-4. Human cytokine microarray and quantitative real-time PCR results indicated that CS1 activation enhanced mRNA transcripts of flt3 ligand, lymphotoxin A, TNF, and IL-14. These results suggest that activation of B lymphocytes through surface CS1 may be mediated through secretion of autocrine cytokines and CS1 may play a role in the regulation of B lymphocytes proliferation during immune responses.