Modulation of antigen receptor signaling by IGtranslocations.

Genes that are deregulated as a result of IG translocation are shown in yellow. Antigen binding to the BCR results in B-cell activation via multiple effectors, including Ras, Btk, JNK, and PLCγ.Pax5: Pax5 transcriptionally up-regulates 2 key molecules in the BCR complex, CD79a and CD19, allowing enhanced B-cell proliferation. FcγRIIB: In normal B cells, FcγRIIB mediates its inhibitory signal via 1 of 2 pathways. (1) Simultaneous cross-linking of FcγRIIB with the BCR by immune complexes results in phosphorylation of the FcγRIIB ITIM and subsequent recruitment of SHIP, which, by hydrolyzing PIP3, results in dissociation from the membrane and, therefore, inactivation of Btk. (2) Alternatively, cross-linking of FcγRIIB alone results in apoptosis mediated via direct activation of Btk. In cases of follicular lymphoma demonstrating the t(1;22)(q22;q11), the t(14;18) is a prior event, resulting in overexpression of BCL2, which blocks apoptosis and may allow proliferative signals to go unhindered.