CS1 (CRACC, CD319) induces proliferation and autocrine cytokine expression on human B lymphocytes

Kyung Lee Jae, Stephen O. Mathew, Swapnil V. Vaidya, Pappanaicken R. Kumaresan, Porunelloor A. Mathew

Research output: Contribution to journalArticle

46 Scopus citations

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 in its cytoplasmic domain whereas CS1-S lacks immunoreceptor tyrosine-based switch motifs. In this study, we show that human B lymphocytes express only the CS1-L isoform, and its expression is up-regulated 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. The effects of CS1 on B cell proliferation were shown on both naive and memory B cells. 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. Neutralizing Abs against lymphotoxin A, TNF-α, and/or flt3 ligand abolished the ability of CS1 on the B cell proliferation. 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 lymphocyte proliferation during immune responses.

Original languageEnglish (US)
Pages (from-to)4672-4678
Number of pages7
JournalJournal of Immunology
Volume179
Issue number7
StatePublished - Oct 1 2007

ASJC Scopus subject areas

  • Immunology

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    Jae, K. L., Mathew, S. O., Vaidya, S. V., Kumaresan, P. R., & Mathew, P. A. (2007). CS1 (CRACC, CD319) induces proliferation and autocrine cytokine expression on human B lymphocytes. Journal of Immunology, 179(7), 4672-4678.