Schneider P, Takatsuka H, Wilson A, Mackay F, Tardivel A, Lens S, Cachero T G, Finke D, Beermann F, Tschopp J
Institute of Biochemistry, BIL Biomedical Research Center, University of Lausanne, Epalinges, Switzerland.
J Exp Med. 2001 Dec 3;194(11):1691-7. doi: 10.1084/jem.194.11.1691.
B cells undergo a complex series of maturation and selection steps in the bone marrow and spleen during differentiation into mature immune effector cells. The tumor necrosis factor (TNF) family member B cell activating factor of the TNF family (BAFF) (BLyS/TALL-1) plays an important role in B cell homeostasis. BAFF and its close homologue a proliferation-inducing ligand (APRIL) have both been shown to interact with at least two receptors, B cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (TACI), however their relative contribution in transducing BAFF signals in vivo remains unclear. To functionally inactivate both BAFF and APRIL, mice transgenic for a soluble form of TACI were generated. They display a developmental block of B cell maturation in the periphery, leading to a severe depletion of marginal zone and follicular B2 B cells, but not of peritoneal B1 B cells. In contrast, mice transgenic for a soluble form of BCMA, which binds APRIL, have no detectable B cell phenotype. This demonstrates a crucial role for BAFF in B cell maturation and strongly suggests that it signals via a BCMA-independent pathway and in an APRIL-dispensable way.
B细胞在分化为成熟免疫效应细胞的过程中，于骨髓和脾脏内经历一系列复杂的成熟和选择步骤。肿瘤坏死因子（TNF）家族成员——TNF家族的B细胞活化因子（BAFF）（BLyS/TALL-1）在B细胞稳态中发挥重要作用。BAFF及其密切同源物增殖诱导配体（APRIL）均已显示与至少两种受体相互作用，即B细胞成熟抗原（BCMA）和跨膜激活剂与亲环素配体相互作用分子（TACI），然而它们在体内转导BAFF信号方面的相对贡献仍不清楚。为了在功能上使BAFF和APRIL失活，构建了可溶性形式TACI的转基因小鼠。它们在外周表现出B细胞成熟的发育阻滞，导致边缘区和滤泡B2 B细胞严重耗竭，但腹膜B1 B细胞未受影响。相比之下，可溶性形式BCMA（可结合APRIL）的转基因小鼠没有可检测到的B细胞表型。这证明了BAFF在B细胞成熟中的关键作用，并强烈表明它通过不依赖BCMA的途径且以不依赖APRIL方式发出信号。
