Article abstract
Nature Immunology 9, 623 - 631 (2008)
Published online: 18 May 2008 | doi:10.1038/ni.1616
SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway
Sebastian Herzog1, Eva Hug1, Sonja Meixlsperger1, Ji-Hye Paik2, Ronald A DePinho2, Michael Reth1 & Hassan Jumaa1
Abstract
Although the essential role of the adaptor protein SLP-65 in pre-B cell differentiation is established, the molecular mechanism underlying its function is poorly understood. In this study, we uncover a link between SLP-65–dependent signaling and the phosphoinositide-3-OH kinase (PI(3)K)–protein kinase B (PKB)–Foxo pathway. We show that the forkhead box transcription factor Foxo3a promotes light chain rearrangement in pre-B cells. Our data suggest that PKB suppresses light chain recombination by phosphorylating Foxo proteins, whereas reconstitution of SLP-65 function counteracts PKB activation and promotes Foxo3a and Foxo1 activity in pre-B cells. Together, these data illuminate a molecular function of SLP-65 and identify a key role for Foxo proteins in the regulation of light chain recombination, receptor editing and B cell selection.
- Max Planck Institute for Immunobiology, 79108 Freiburg, Germany, and Centre for Biological Signalling Studies (BIOSS) at the Faculty of Biology, Albert-Ludwigs University of Freiburg, 79104 Freiburg, Germany.
- Center for Applied Cancer Science, Departments of Medical Oncology, Medicine and Genetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Correspondence to: Hassan Jumaa1 e-mail: jumaa@immunbio.mpg.de
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