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

Background: 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. Methods: 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 naive (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. Results: 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. Conclusions: 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.

Identiferoai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/627195
Date15 February 2018
CreatorsCentuori, Sara M., Gomes, Cecil J., Kim, Samuel S., Putnam, Charles W., Larsen, Brandon T., Garland, Linda L., Mount, David W., Martinez, Jesse D.
ContributorsUniv Arizona, Canc Ctr, Univ Arizona, Canc Biol Grad Interdisciplinary Program, Univ Arizona, Dept Surg, Univ Arizona, Dept Med, Div Hematol Oncol, Univ Arizona, Dept Mol & Cellular Biol, Univ Arizona, Cell & Mol Med
PublisherBIOMED CENTRAL LTD
Source SetsUniversity of Arizona
LanguageEnglish
Detected LanguageEnglish
TypeArticle
Rights© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.
Relationhttps://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1404-z

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