S1PR₄ deficiency results in reduced germinal center formation but only marginally affects antibody production

Introduction: Splenic B cells exhibit a high expression of the G protein-coupled sphingosine-1-phosphate (S1P) receptor type 4 (S1PR₄). Little is known about the functional relevance of S1PR₄ expression on those cells.

Methods: In this study, S1PR₄-deficient mice were used to study the role of S1PR₄-mediated S1P signaling in B cell motility in vitro and for the maintenance of the splenic architecture under steady state conditions as well as in polymicrobial abdominal sepsis in vivo. Finally, the impact of S1PR₄ deficiency on antibody production after immunization with T cell dependent antigens was assessed.

Results: Loss of S1PR₄ resulted in minor alterations of the splenic architecture concerning the presence of B cell follicles. After sepsis induction, the germinal center response was severely impaired in S1PR₄-deficient animals. Splenic B cells showed reduced motility in the absence of S1PR₄. However, titres of specific antibodies showed only minor reductions in S1PR₄-deficient animals.

Discussion: These observations suggest that S1P signaling mediated by S1PR₄ modifies chemokine-induced splenic B cell chemotaxis, thus modulating splenic microarchitecture, GC formation and T-cell dependent antibody production.