The Francis Crick Institute, London NW1 1AT, UK.
The Francis Crick Institute, London NW1 1AT, UK; Department of Immunology & Inflammation, Imperial College London, London W12 0NN, UK.
Curr Opin Immunol. 2021 Aug;71:124-131. doi: 10.1016/j.coi.2021.06.014. Epub 2021 Aug 2.
BAFF is a critical cytokine supporting the survival of mature naïve B cells, acting through the BAFFR receptor. Recent studies show that BAFF and BAFFR are also required for the survival of memory B cells, autoimmune B cells as well as malignant chronic lymphocytic leukaemia (CLL) cells. BAFFR cooperates with other receptors, notably the B cell antigen receptor (BCR), a process which is critical for the expansion of autoimmune and CLL cells. This crosstalk may be mediated by TRAF3 which interacts with BAFFR and with CD79A, a signalling subunit of the BCR and the downstream SYK kinase, inhibiting its activity. BAFF binding to BAFFR leads to degradation of TRAF3 which may relieve inhibition of SYK activity transducing signals to pathways required for B cell survival. BAFFR activates both canonical and non-canonical NF-κB signalling and both pathways play important roles in the survival of B cells and CLL cells.
BAFF 是一种关键的细胞因子，通过 BAFFR 受体支持成熟初始 B 细胞的存活。最近的研究表明，BAFF 和 BAFFR 对于记忆 B 细胞、自身免疫性 B 细胞以及恶性慢性淋巴细胞白血病（CLL）细胞的存活也是必需的。BAFFR 与其他受体（特别是 B 细胞抗原受体（BCR））合作，这一过程对于自身免疫和 CLL 细胞的扩增至关重要。这种串扰可能是由 TRAF3 介导的，它与 BAFFR 以及 BCR 的信号亚基 CD79A 相互作用，抑制其活性。BAFF 与 BAFFR 的结合导致 TRAF3 的降解，这可能解除对 SYK 活性的抑制，从而将信号转导至 B 细胞存活所需的途径。BAFFR 激活经典和非经典 NF-κB 信号通路，这两条通路在 B 细胞和 CLL 细胞的存活中都发挥着重要作用。
