美国华盛顿大学医学院Marion Pepper小组近日取得一项新成果。经过不懈努力，他们的研究显示，白介素4下调转录因子BCL6促进生发中心记忆性B细胞的选择。2024年3月20日出版的《免疫》发表了这项成果。

该课题组研究人员发现，生发中心B细胞中的白介素4细胞因子信号通过负向自动调节直接下调转录因子BCL6，从而使细胞从生发中心进程中释放出来，并促进记忆B细胞的形成。这个选择事件需要额外的生存线索，因此可能导致生发中心退出或死亡。

课题组研究人员证明，增加白介素4的生物利用度或限制白介素4信号传导都会破坏记忆B细胞选择的严格性。通过这种方式，白介素4对BCL6表达的控制作为生发中心内的可调节开关，严格调节记忆B细胞的选择和亲和成熟。

据悉，生发中心(GC)来源的记忆B细胞(MBCs)在再次感染时分化为保护性抗体分泌细胞，对体液免疫至关重要。生发中心的形成和生发中心内的细胞相互作用已被详细研究，但允许MBCs选择和退出的确切信号尚不清楚。

附：英文原文

Title: Interleukin-4 downregulates transcription factor BCL6 to promote memory B cell selection in germinal centers

Author: Laila Shehata, Christopher D. Thouvenel, Brian D. Hondowicz, Lucia A. Pew, Gretchen Harms Pritchard, David J. Rawlings, Jinyong Choi, Marion Pepper

Issue&Volume: 2024-03-20

Abstract: Germinal center (GC)-derived memory B cells (MBCs) are critical for humoral immunityas they differentiate into protective antibody-secreting cells during re-infection.GC formation and cellular interactions within the GC have been studied in detail,yet the exact signals that allow for the selection and exit of MBCs are not understood.Here, we showed that IL-4 cytokine signaling in GC B cells directly downregulatedthe transcription factor BCL6 via negative autoregulation to release cells from theGC program and to promote MBC formation. This selection event required additionalsurvival cues and could therefore result in either GC exit or death. We demonstratethat both increasing IL-4 bioavailability or limiting IL-4 signaling disrupted MBCselection stringency. In this way, IL-4 control of BCL6 expression serves as a tunableswitch within the GC to tightly regulate MBC selection and affinity maturation.

DOI: 10.1016/j.immuni.2024.02.018

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00094-3