Novel neurotrophin-1/B cell-stimulating factor-3: A cytokine of the IL-6 family

We have identified a cytokine of the IL-6 family and named it novel neurotr ophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3). NNT-1/BSF-3 cDNA was clo ned from activated Jurkat human T cell lymphoma cells. Its sequence predict s a 225-aa protein with a 27-aa signal peptide, a molecular mass of 22 kDa in mature form, and the highest homology to cardiotrophin-1 and ciliary neu rotrophic factor. The gene for NNT-1/BSF-3 is on chromosome 11q13. A murine equivalent to NNT-1/BSF-3 also was identified, which shows 96% homology to human NNT-1/BSF-3. NNT-1/BSF-3 mRNA is found mainly in lymph nodes and spl een. NNT-1/BSF-3 induces tyrosine phosphorylation of glycoprotein 130 (gp13 0), leukemia inhibitory factor receptor beta, and signal transducer and act ivator of transcription 3 in the SK-N-MC human neuroblastoma cells. NNT-1/B SF3 shows activities typical of IL-6 family members. In vitro, it supports the survival of chicken embryo motor and sympathetic neurons. In mice, it i nduces serum amyloid A, potentiates the induction by IL-1 of corticosterone and IL-6, and causes body weight loss and B cell hyperplasia with serum Ig G and IgM increase. NNT-1/BSF3 is a gp130 activator with B-cell stimulating capability.