The Effect Of CD40 Signaling And Of Related Molecules On The Biological Behavior Of Multiple Myeloma

The stimulation of CD40 can induce many biological effects on B cells. CD40 signaling is essential for thymus-dependent induction of immunoglobulin isotype synthesis itself as well as for the switching of the isotype of the heavy chain,. Ligation of CD40 mediates a broad variety of immune and inflammatory responses, such as the expression of adhesion molecules (CD23, B7, CD54, CD95 et al), cytokines (IL-2, IL-6, IL-8, TNFa, GM-CSF et al), matrix-degrading enzymes and apoptotic mediators. CD40 on the malignant B lymphocytes can trigger cell proliferation, growth arrested or apoptosis, but the exact biological behavior is unclear. However, recent studies suggested that in B lymphocytes TRAFs, JAK3 and ERKs are essential for CD40 signaling. Among them, TRAFs are the most importantadaptor protein.Our result show: (1) Co-incubation with the three stimulators induced a significant inhibition of cell growth of XG2 with Gl-phase arrest in vitro. Interestingly, we also found that the two kinds (cross-linking and ligation) of CD40 stimulators induced XG2 cells to apoptosis in vitro. The apoptotic rate for XG2 was 23.3%(CD40mAb), 18.9%(CD40L-TC) and 24.5%(rhsCD40L) respectively; (2) TRAF1, TRAF2, TRAF5, TRAF6 was downregulated after XG2 was triggered by CD40, while TRAF 1,5,6 was upregulated in XG7; (3) low concentrations of 5C11 induced proliferation of XG2, while high concentrations of 5C11 resulted in homotypic aggregation of XG2, strongly suppressed its proliferation and led to apoptosis after 24 hours of treatment. This effect is attributed to upregulate expression of the membrane-associated TNF(mTNF) and TNFR1. All these results have been conformed by our researching in primary myeloma cells. Conclusion: The behavior diversity of CD40 signal on MM cells may be related to the type and intensity of CD40...