Benson Micah J, Dillon Stacey R, Castigli Emanuela, Geha Raif S, Xu Shengli, Lam Kong-Peng, Noelle Randolph J
Department of Microbiology and Immunology, Dartmouth Medical School, The Norris Cotton Cancer Center, Lebanon, NH 03756, USA.
J Immunol. 2008 Mar 15;180(6):3655-9. doi: 10.4049/jimmunol.180.6.3655.
Memory B (B(MEM)) cells and long-lived bone marrow plasma cells (BM-PCs) persist within local environmental survival niches that afford cellular longevity. However, the factors supporting B(MEM) cell survival within the secondary lymphoid organs and allowing BM-PC persistence in the bone marrow remain poorly characterized. We report herein that long-lived B(MEM) cell survival and function are completely independent of BAFF (B cell-activating factor of the TNF family) or APRIL (a proliferation-inducing ligand). Thus, B(MEM) cells represent the only mature B2 lineage subset whose survival is independent of these ligands. We have previously shown that the TNFR family member receptor BCMA (B cell maturation Ag) is a critical survival receptor for BM-PC survival in vivo. We identify in this study the ligands critical for BM-PC survival and show that either BAFF or APRIL supports the survival of BM-PCs in vivo. These data define the BAFF/APRIL-dependent and -independent components of long-lived humoral immunity.
记忆B（B(MEM)）细胞和长寿骨髓浆细胞（BM-PCs）存在于能赋予细胞长寿能力的局部环境存活龛中。然而，支持B(MEM)细胞在二级淋巴器官中存活以及使BM-PCs在骨髓中持续存在的因素仍未得到充分表征。我们在此报告，长寿B(MEM)细胞的存活和功能完全独立于BAFF（肿瘤坏死因子家族的B细胞活化因子）或APRIL（增殖诱导配体）。因此，B(MEM)细胞是唯一存活独立于这些配体的成熟B2谱系亚群。我们之前已表明，TNFR家族成员受体BCMA（B细胞成熟抗原）是体内BM-PCs存活的关键存活受体。我们在本研究中确定了对BM-PCs存活至关重要的配体，并表明BAFF或APRIL在体内均支持BM-PCs的存活。这些数据界定了长寿体液免疫中依赖和不依赖BAFF/APRIL的成分。
