In the third tramsgenic model, overexpression of APRIL (a proliferation inducing ligand ) in murine T cells leads indirectly to B-cell proliferation and survival because of signaling through its receptors BCMA and TACI. Unlike the previous two transgenic animals, however, expansion of CD5 B cells occur in only 40% of animals, with these B cells locating predominantly in the spleen and rarely passing into the blood. Nevertheless, as APRIL's action involves the TRAFs and leads to NFκB activation, this model may prove helpful in linking signals from soluble ligands and surface receptors to the NFκB pathway, a pathway known to be constitutively active in some B-CLL clones.
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