Research ArticleImmunology

The Tetraspanin CD37 Orchestrates the α4β1 Integrin–Akt Signaling Axis and Supports Long-Lived Plasma Cell Survival

Sci. Signal.  13 Nov 2012:
Vol. 5, Issue 250, pp. ra82
DOI: 10.1126/scisignal.2003113

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CD37 Stimulates Plasma Cell Survival

To generate immunological memory, B cells with high-affinity immunoglobulin receptors proliferate and differentiate in germinal centers in the spleen to produce memory B cells and long-lived antibody-secreting cells known as plasma cells. van Spriel et al. found that mice deficient in the tetraspanin protein CD37 had defective antibody production and decreased numbers of germinal center B cells compared to those in wild-type mice, which was a result of enhanced apoptosis. Survival signals in B cells were initiated by engagement of the integrin α4β1 and activation of the downstream kinase Akt. In the absence of CD37, integrin clustering and function were impaired, and activation of the Akt survival pathway was defective. Thus, long-lived plasma cells rely on the tetraspanin CD37 to enable integrin-Akt survival signaling.