Double-negative (CD27 - IgD - ) B cells are expanded in NSCLC and inversely correlate with affinity-matured B cell populations

• Published in: Journal of translational medicine 2018-02, Vol.16 (1), p.30-30, Article 30
• Main Authors: Centuori, Sara M, Gomes, Cecil J, Kim, Samuel S, Putnam, Charles W, Larsen, Brandon T, Garland, Linda L, Mount, David W, Martinez, Jesse D
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Analysis; Antibody Affinity - immunology; B cells; B-Lymphocytes - pathology; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - pathology; CD27; Cell Proliferation; Diagnosis; Double-negative B cells; Female; Health aspects; Humans; Immunoglobulin D - metabolism; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Male; Middle Aged; NSCLC; TIL-Bs; Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism
• ISSN: 1479-5876; 1479-5876
• 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 CD79A CD27 IgD . These CD27 IgD (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 (CD27 IgD ), affinity-matured (CD27 IgD ), early memory/germinal center cells (CD27 IgD ) or double-negative B cells (CD27 IgD ). 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 CD27 IgD double-negative B cells in human NSCLC and that this population is inversely correlated with traditional affinity-matured B cell populations.