Multiplex B Cell Characterization in Blood, Lymph Nodes, and Tumors from Patients with Malignancies
2013 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 190, no 11, 5847-5855 p.Article in journal (Refereed) Published
B lymphocytes contribute to immune surveillance, by tumor-specific Abs and Ag presentation to T lymphocytes, but are insufficiently studied in humans. In this article, we report a flow cytometric investigation of B lymphocyte subpopulations in blood, lymph nodes (LNs), and malignant tissues from 20 patients operated on because of advanced solid tumors. The CD19(+) compartment in peripheral blood was essentially unaltered in patients, as compared with healthy control subjects. In metastatic LNs, signs of B lymphocyte activation were observed, as evidenced by increased proportions of plasmablasts and CD86-expressing cells. In tumor-infiltrating B lymphocytes (TIL-B), both switched memory cells and plasmablasts were expanded, as compared with nonmalignant epithelium. Moreover, pronounced skewing of Ig lambda/Ig kappa ratio was evident among TIL-Bs. By spectratype analysis on IgH, we confirmed a monoclonal expansion of the Vh7 family in TIL-B, also present in a tumor-associated LN. Sequencing the clonally expanded Vh7 revealed signs of somatic hypermutation. In conclusion, B lymphocytes in cancer patients exhibit signs of activation in tumor-associated tissues, likely induced by recognition of tumor Ags. Increased numbers of switched memory cells and plasmablasts in combination with clonal expansion and signs of somatic hypermutation suggest a CD4(+) T lymphocyte-dependent antitumoral response, which may be exploited for immunotherapy.
Place, publisher, year, edition, pages
2013. Vol. 190, no 11, 5847-5855 p.
Cancer and Oncology
IdentifiersURN: urn:nbn:se:umu:diva-76793DOI: 10.4049/jimmunol.1203279ISI: 000319205900056OAI: oai:DiVA.org:umu-76793DiVA: diva2:637154