Zhang Xu Hannah, Yin Zhirong, Zhang Aimin, Pillai Raju, Armstrong Brian, Rosen Steven T
Department of Hematology City of Hope National Medical Center Duarte California USA.
Department of Pathology Solid Tumor Core City of Hope National Medical Center Duarte California USA.
EJHaem. 2020 Jun 29;1(1):300-303. doi: 10.1002/jha2.50. eCollection 2020 Jul.
Lymph nodes are important front-line defense immune tissues, which also act against inflammatory diseases and cancer. Lymph nodes undergo extensive upheavals within newly formed germinal centers (GCs) when exposed to antigens, the molecular mechanisms of which remain elusive. Recently, p38γ was identified as an important target for multiple cancers, including cutaneous T-cell lymphoma (CTCL). We previously observed that p38γ is overexpressed in CTCL versus normal cells, but it is not clear if p38γ is expressed in B or T lymphocytes of GCs of patients in response to a stress such as cancer. Therefore, in this study, we obtained non-metastatic reactive lymph nodes adjacent to cancer lesions (colorectal adenocarcinoma), then performed multicolor immunohistochemical staining for p38γ and other relevant markers. We observed for the first time that p38γ was expressed in the light zone of activated B cells and T helper cells in GCs, whereas DNA-methyltransferase 1 (DNMT1), a marker for GC B cells, was highly expressed in centrocytes and in the dark zone of GCs. This inverse relationship suggests a novel function for p38γ in T cells that cross-talk to B cells in response to stress.
淋巴结是重要的一线防御免疫组织，也参与对抗炎症性疾病和癌症。当暴露于抗原时，淋巴结在新形成的生发中心（GCs）内会经历广泛的变化，但其分子机制仍不清楚。最近，p38γ被确定为包括皮肤T细胞淋巴瘤（CTCL）在内的多种癌症的重要靶点。我们之前观察到，与正常细胞相比，p38γ在CTCL中过度表达，但尚不清楚p38γ是否在癌症等应激反应下患者GCs的B淋巴细胞或T淋巴细胞中表达。因此，在本研究中，我们获取了与癌症病变（结肠直肠腺癌）相邻的非转移性反应性淋巴结，然后对p38γ和其他相关标志物进行了多色免疫组织化学染色。我们首次观察到，p38γ在GCs中活化B细胞和T辅助细胞的亮区表达，而作为GC B细胞标志物的DNA甲基转移酶1（DNMT1）在中心细胞和GCs的暗区高度表达。这种反向关系表明p38γ在T细胞中具有一种新功能，即响应应激与B细胞进行相互作用。
