Schematic representation of t(14;18)+B-cell clones and the genesis of follicular lymphoma. Defective VDJ recombination leads to the t(14;18) translocation and aberrant BCL2 protein expression. Recent work by Roulland and colleagues52 suggests that antigen stimulation allows the t(14;18)+ B-cell in normal healthy individuals to enter the germinal center and undergo the germinal center reaction. Ectopic expression of BCL2 in the germinal center favors extended B-cell survival such that additional genetic changes are acquired by this B cell and may ultimately result in transformation to follicular lymphoma. In addition, N-glycosylation sites in Ig V regions by directly binding oligomannose sugars could modulate B-cell receptor-mediated signaling and contribute to follicular lymphoma pathogenesis.
