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Beyond transitional selection: New roles for BLyS in peripheral tolerance

Michael A Oropallo1, Kerstin Kiefer, Ann Marshak-Rothstein

  • 1Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104-6082.

Drug Development Research
|February 11, 2012
PubMed

B cell targeted therapies have enjoyed recent success in the treatment of systemic autoimmune diseases. Among these, Belimumab, which blocks the B cell survival cytokine BLyS, was recently approved for the treatment of Systemic Lupus Erythematosus. It is therefore important to consider the roles BLyS plays in B cell tolerance. Herein, we review how BLyS contributes to the negative selection of autoreactive B cell clones from the preimmune repertoire as well as its role in regulating both germinal center and extrafollicular peripheral B cell responses. We further examine the complex role of Toll-like receptors (TLRs) in humoral autoimmunity, pointing out potential crosstalk between BLyS and TLR pathways.

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