Editors' ChoiceImmunology

The Plasma Cell Fountain of Youth?

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Science Translational Medicine  27 Feb 2013:
Vol. 5, Issue 174, pp. 174ec35
DOI: 10.1126/scitranslmed.3005906

Understanding the secrets to a long life may be simple, such as not smoking, or more complicated, such as following the Okinawa diet. For plasma cells, the secrets to longevity have definitely fallen in the more complicated category; however, these secrets get to the core of improving vaccines and treating autoimmunity. Peperzak et al. have identified an antiapoptotic molecule that appears critical for the long life of plasma cells. This molecule, Mcl-1, may serve as a marker for these specialized B cells and could be exploited to extend the longevity of vaccine-stimulated plasma cells and to truncate the life span of pathogenic plasma cells.

Plasma cells are rare, terminally differentiated B cells that churn out antibody throughout their long life span. The central role of antibodies in host protection and autoimmunity has made the study of plasma cells a focus of many labs. Peperzak et al. studied antiapoptotic molecules in several knockout mice that were deficient in plasma cells. The most severe phenotype was noted in mice that lacked BCMA, a cell-surface cytokine receptor. Lack of this receptor was associated with less plasma cell expression of Mcl-1, a member of the Bcl-2 family of antiapoptotic proteins. The authors then confirmed the relevance of plasma cell Mcl-1 expression in vivo using temporally controlled deletion of the molecule specifically in plasma cells.

Unraveling the complexity of antibody expression and maintenance is a central question in vaccine development and autoimmunity. This work adds to our understanding of the factors required for the long-term maintenance of plasma cells. Further work needs to validate these findings beyond model systems, but knowing the secret of Mcl-1 may allow us to modulate the life span of plasma cells in order to enhance or eliminate antibody secretion.

V. Peperzak et al., Mcl-1 is essential for the survival of plasma cells. Nat. Immunol. 14, 290–297 (2013). [Abstract]

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