Long-term humoral immunity requires memory B cells and long-lived antibody-secreting cells (ASCs). In Science Signaling, van Spriel et al. show that optimal long-term immunoglobulin G responses require the tetraspanin protein CD37. There is abundant CD37 on the surface of mature B cells, which seems to be necessary for clustering of the integrin α4β1, required for high-affinity binding to its ligand, VCAM-1. The VCAM-1–α4β1 interaction triggers an outside-in signaling cascade that activates the kinase Akt, which in turn phosphorylates and inactivates the proapoptotic molecule Bad. CD37-deficient mice develop germinal centers after immunization but produce less antibody and have fewer immunoglobulin G–producing plasma cells than do wild-type mice. These data suggest CD37-induced clustering of α4β1 contributes to the long-term survival of plasma cells.

Sci. Signal. (13 November 2012) doi:10.1126/scisignal.2003113