TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, Elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase

BCMA (B cell maturation) is a nonglycosylated integral membrane type I prot ein that is preferentially expressed in mature B lymphocytes. Previously, w e reported in a human malignant myeloma cell line that BCMA is not primaril y present on the cell surface but lies in a perinuclear structure that part ially overlaps the Golgi apparatus. We now show that in transiently or stab ly transfected cells, BCMA is located on the cell surface, as well as in a perinulear Golgi-like structure. We also show that overexpression of BCMA i n 293 cells activates NF-kappa B, Elk-1, the c-Jun N-terminal kinase, and t he p38 mitogen-activated protein kinase, Coimmunoprecipitation experiments performed in transfected cells showed that BCMA associates with TNFR-associ ated factor (TPAF) 1, TRAF2, and TRAF3 adaptor proteins. Analysis of deleti on mutants of the intracytoplasmic tail of BCMA showed that the 25-aa prote in segment, from position 119 to 143, conserved between mouse and human BCM A, is essential for its association with the TRAFs and the activation of NF -kappa B, Elk-1, and c-Jun N-terminal kinase. BCMA belongs structurally to the TNFR family. Its unique TNFR moth corresponds to a variant motif presen t in the fourth repeat of the TNFRI molecule, This study confirms that BCMA is a functional member of the TNFR superfamily. Furthermore, as BCMA is la cking a "death domain" and its overexpression activates NF-kappa B and c-Ju n N-terminal kinase, we can reasonably hypothesize that upon binding of its corresponding ligand BCMA transduces signals for cell survival and prolife ration.