Lipoxin B₄ Enhances Human Memory B Cell Antibody Production via Upregulating Cyclooxygenase-2 Expression

Vaccination has been the most effective way to prevent or reduce infectious diseases; examples include the eradication of smallpox and attenuation of tetanus and measles. However, there is a large segment of the population that responds poorly to vaccines, in part because they are immunocompromised because of disease, age, or pharmacologic therapy and are unable to generate long-term protection. Specialized proresolving mediators are endogenously produced lipids that have potent proresolving and anti-inflammatory activities. Lipoxin B₄ (LXB₄) is a member of the lipoxin family, with its proresolving effects shown in allergic airway inflammation. However, its effects on the adaptive immune system, especially on human B cells, are not known. In this study, we investigated the effects of LXB₄ on human B cells using cells from healthy donors and donors vaccinated against influenza virus in vitro. LXB₄ promoted IgG Ab production in memory B cells and also increased the number of IgG-secreting B cells. LXB₄ enhanced expression of two key transcription factors involved in plasma cell differentiation, BLIMP1 and XBP1. Interestingly, LXB₄ increased expression of cyclooxygenase-2 (COX2), an enzyme that is required for efficient B cell Ab production. The effects of LXB₄ are at least partially COX2-dependent as COX2 inhibitors attenuated LXB₄-stimulated BLIMP1 and Xpb-1 expression as well as IgG production. Thus, our study reveals for the first time, to our knowledge, that LXB₄ boosts memory B cell activation through COX2 and suggests that LXB₄ can serve as a new vaccine adjuvant.