Abstract
Accumulating evidence suggests that Gα13 signaling by G protein-coupled receptors negatively regulate B cell function. We report here that lysophosphatidylserine (LysoPS), an emerging immunoregulatory lysophospholipid, is produced upon B cell activation and suppresses B cell adhesive properties via its Gα13-coupled receptors, LPS2 and LPS2L. B cell activation in vitro markedly increased the LysoPS level thereby inhibiting cell aggregation in a LysoPS receptor-dependent manner. In T cell-dependent antigen immunization and asthma models, LPS2/2L double knock-out mice exhibited increased B cell number with early and enhanced formation of germinal center (GC) and tertiary lymphoid structures (TLS)-like structures, in addition to an elevated antibody level and worsened conditions. We thus propose a novel regulatory mechanism for lymphocyte aggregation in which LysoPS on B cells acts in an autocrine/paracrine fashion to inhibit GC and TLS formation by disrupting B cell-B cell or B cell-T cell interactions via Gα13 signaling.