Activation of NF-κB and chromosomal translocations found in MALT lymphoma. Epitopes from Helicobacter pylori can lead to activation of NF-κB through the B-cell receptor (BCR) via receptor-associated tyrosine kinases of the SRC and SYK family, which signal a protein kinase C (PKC) family member to oligomerize BCL-10, CARMA1, and MALT1 leading to activation of the inhibitor of NF-κB kinase (IKK) complex. The IKK complex phosphorylates the inhibitor of NF-κB (IκB) prompting its degradation by the proteasome and allowing the NF-κB family members to translocate to the nucleus and control NF-κB–dependent gene expression. The t(1;14) and t(14;18) translocations lead to overexpression of the BCL10 and MALT1 genes respectively and the t(11;18) translocation produces a chimeric API2-MALT1 protein that can directly activate the IKK complex. Constitutive activation of the NF-κB pathway by these translocations bypasses the requirement for BCR signaling and may account for the antigen independence of cells harboring these translocations.