Within inflammatory environments, B cells encountering foreign or self-Ag can develop tertiary lymphoid tissue expressing activation-induced
cytosine deaminase (AID). Recently, this
DNA-modifying
enzyme was detected in nonlymphoid cells within several inflamed tissues and strongly implicated in malignant transformation. This study examines whether a
cyclooxygenase 2 (COX-2) pathway, often linked to
inflammation, influences AID expression in activated B lymphocytes. In this paper, we report that dividing human B cells responding to surrogate C3d-coated Ag,
IL-4, and BAFF express AID, as well as COX-2. A progressive increase in AID with each division was paralleled by a division-related increase in a COX-2-linked
enzyme, microsomal
PGE(2) synthase-1, and the
PGE(2)R, EP2. Cells with the greatest expression of AID expressed the highest levels of EP2. Although
COX-2 inhibitors diminished both AID expression and
IgG class switching, exogenous
PGE(2) and
butaprost, a selective EP2 agonist, augmented AID
mRNA/
protein and increased the numbers of
IgG(+) progeny. Despite the latter, the proportion of
IgG(+) cells within viable progeny generally declined with
PGE(2) supplementation. This was not due to PGE(2)-promoted differentiation to plasma cells or to greater downstream switching. Rather, because phosphorylated
ataxia telangiectasia mutated levels were increased in progeny of PGE(2)-supplemented cultures, it appears more likely that
PGE(2) facilitates AID-dependent
DNA double-strand breaks that block B cell cycle progression or promote activation-induced cell death, or both. Taken together, the results suggest that a
PGE(2) feed-forward mechanism for augmenting COX-2 pathway
proteins promotes progressively increased levels of AID
mRNA,
protein, and function.