The role of Cox‐2 in B cell development and function

Cyclooxygenase (COX) is the rate‐limiting enzyme that catalyzes the conversion of arachadonic acid into prostaglandins. Significantly, COX‐2 is the predominant isoform contributing to the high PGE 2 levels in chronic inflammatory conditions including many autoimmune disorders. This project will not only shed lights on the mechanisms of COX‐2 action in B cell response but also provide critical guidance for the clinical application of COX‐2 inhibitors. Hypothesis: COX‐2 plays an important role in regulating B cell development, activation and function. B cell‐specific manipulation of COX‐2 expression will lead to altered B cell activation and function. We aim to determine the mechanisms of Cox‐2 regulation in B cell development and function by defining the differential expression of Cox‐2 during B cell development, in different B cell subsets, and in B cells activated by various innate and adaptive stimuli. Sorted B cell subsets, and MACS purified B cells, from naïve C57Bl/6 mice were analyzed for Cox‐2 expression by qRT‐PCR. The B cell subsets Pro‐B, Pre‐B, Immature, Mature, Transitional 1 and 2, marginal zone, B1a and B1b, do not express Cox‐2 ex‐vivo . However, our data shows that the magnitude of B cell Cox‐2 expression is differentially induced by TLR4, BCR cross‐linking and CD40 activation. These results suggest a role for Cox‐2 in B cell function.