EMBO Journal 2015-04-01

CD19 and BAFF-R can signal to promote B-cell survival in the absence of Syk.

Elias Hobeika, Ella Levit-Zerdoun, Vasiliki Anastasopoulou, Roland Pohlmeyer, Simon Altmeier, Ameera Alsadeq, Marc-Werner Dobenecker, Roberta Pelanda, Michael Reth

Index: EMBO J. 34(7) , 925-39, (2015)

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Abstract

The development and function of B lymphocytes is regulated by numerous signaling pathways, some emanating from the B-cell antigen receptor (BCR). The spleen tyrosine kinase (Syk) plays a central role in the activation of the BCR, but less is known about its contribution to the survival and maintenance of mature B cells. We generated mice with an inducible and B-cell-specific deletion of the Syk gene and found that a considerable fraction of mature Syk-negative B cells can survive in the periphery for an extended time. Syk-negative B cells are defective in BCR, RP105 and CD38 signaling but still respond to an IL-4, anti-CD40, CpG or LPS stimulus. Our in vivo experiments show that Syk-deficient B cells require BAFF receptor and CD19/PI3K signaling for their long-term survival. These studies also shed a new light on the signals regulating the maintenance of the normal mature murine B-cell pool.© 2015 The Authors.