University of Arizona Cancer Center, University of Arizona, 1515 N. Campbell Ave., Tucson, AZ, 85724, USA.
Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ, 85724, USA.
J Transl Med. 2018 Feb 15;16(1):30. doi: 10.1186/s12967-018-1404-z.
The presence of B cells in early stage non-small cell lung cancer (NSCLC) is associated with longer survival, however, the role these cells play in the generation and maintenance of anti-tumor immunity is unclear. B cells differentiate into a variety of subsets with differing characteristics and functions. To date, there is limited information on the specific B cell subsets found within NSCLC. To better understand the composition of the B cell populations found in NSCLC we have begun characterizing B cells in lung tumors and have detected a population of B cells that are CD79ACD27IgD. These CD27IgD (double-negative) B cells have previously been characterized as unconventional memory B cells and have been detected in some autoimmune diseases and in the elderly population but have not been detected previously in tumor tissue.
A total of 15 fresh untreated NSCLC tumors and 15 matched adjacent lung control tissues were dissociated and analyzed by intracellular flow cytometry to detect the B cell-related markers CD79A, CD27 and IgD. All CD79A B cells subsets were classified as either naïve (CD27IgD), affinity-matured (CD27IgD), early memory/germinal center cells (CD27IgD) or double-negative B cells (CD27IgD). Association of double-negative B cells with clinical data including gender, age, smoking status, tumor diagnosis and pathologic differentiation status were also examined using the logistic regression analysis for age and student's t-test for all other variables. Associations with other B cell subpopulations were examined using Spearman's rank correlation.
We observed that double-negative B cells were frequently abundant in lung tumors compared to normal adjacent controls (13 out of 15 cases), and in some cases made up a substantial proportion of the total B cell compartment. The presence of double-negative cells was also found to be inversely related to the presence of affinity-matured B cells within the tumor, Spearman's coefficient of - 0.76.
This study is the first to observe the presence of CD27IgD double-negative B cells in human NSCLC and that this population is inversely correlated with traditional affinity-matured B cell populations.
早期非小细胞肺癌（NSCLC）中 B 细胞的存在与更长的生存时间相关，然而，这些细胞在抗肿瘤免疫的产生和维持中所起的作用尚不清楚。B 细胞可分化为具有不同特征和功能的多种亚群。迄今为止，关于 NSCLC 中发现的特定 B 细胞亚群的信息有限。为了更好地了解 NSCLC 中发现的 B 细胞群体的组成，我们已经开始对肺肿瘤中的 B 细胞进行特征描述，并检测到一群 CD79ACD27IgD 的 B 细胞。这些 CD27IgD（双阴性）B 细胞以前被描述为非常规记忆 B 细胞，已在一些自身免疫性疾病和老年人群中检测到，但以前未在肿瘤组织中检测到。
共分离和分析了 15 例未经治疗的新鲜 NSCLC 肿瘤和 15 例匹配的相邻肺对照组织，通过细胞内流式细胞术检测 B 细胞相关标志物 CD79A、CD27 和 IgD。所有 CD79A B 细胞亚群均分为幼稚（CD27IgD）、亲和力成熟（CD27IgD）、早期记忆/生发中心细胞（CD27IgD）或双阴性 B 细胞（CD27IgD）。使用逻辑回归分析年龄和学生 t 检验所有其他变量，对双阴性 B 细胞与包括性别、年龄、吸烟状况、肿瘤诊断和病理分化状态在内的临床数据之间的关联进行了研究。使用 Spearman 秩相关分析对与其他 B 细胞亚群的关联进行了研究。
我们观察到，与正常相邻对照相比，双阴性 B 细胞在肺肿瘤中经常丰富（15 例中有 13 例），并且在某些情况下，占总 B 细胞区室的很大比例。还发现双阴性细胞的存在与肿瘤内亲和力成熟的 B 细胞的存在呈负相关，Spearman 系数为-0.76。
这项研究首次观察到 CD27IgD 双阴性 B 细胞存在于人类 NSCLC 中，并且该群体与传统亲和力成熟的 B 细胞群体呈负相关。
