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¹ Department of Immunology and ² Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada
³ Campbell Family Institute for Cancer Research, Princess Margaret Hospital, Toronto, Ontario M5G 2C1, Canada
⁴ Technische Universität München, 81675 Munich, Germany

CORRESPONDENCE Tak W. Mak: tmak{at}uhnresearch.ca OR Jennifer L. Gommerman: jen.gommerman{at}utoronto.ca

B cell activation factor of the TNF family (BAFF) activates noncanonical nuclear factor B (NF-B) heterodimers that promote B cell survival. We show that although MALT1 is largely dispensable for canonical NF-B signaling downstream of the B cell receptor, the absence of MALT1 results in impaired BAFF-induced phosphorylation of NF-B2 (p100), p100 degradation, and RelB nuclear translocation in B220⁺ B cells. This corresponds with impaired survival of MALT1^–/– marginal zone (MZ) but not follicular B cells in response to BAFF stimulation in vitro. MALT1^–/– MZ B cells also express higher amounts of TRAF3, a known negative regulator of BAFF receptor–mediated signaling, and TRAF3 was found to interact with MALT1. Furthermore, phenotypes associated with overexpression of BAFF, including increased MZ B cell numbers, elevated serum immunoglobulin titers, and spontaneous germinal center formation, were found to be dependent on B cell–intrinsic MALT1 expression. Our results demonstrate a novel role for MALT1 in biological outcomes induced by BAFF-mediated signal transduction.

Abbreviations used: BAFF, B cell activation factor of the TNF family; BCMA, B cell maturation antigen; CGG, chicken -globulin; FO, follicular; GC, germinal center; IKK, IB kinase; MZ, marginal zone; NIK, NF-B–inducing kinase; PI, propidium iodide; PI3-kinase, phosphoinositide 3-kinase; TACI, transmembrane activator and calcium modulator and cyclophilin ligand interactor; Td, T dependent; Ti, T independent.

© 2009 Tusche et al.
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