Multiplex B Cell Characterization in Blood, Lymph Nodes, and Tumors from Patients with Malignancies

• Published in: The Journal of immunology (1950) Vol. 190; no. 11; pp. 5847 - 5855
• Main Authors: Zirakzadeh, A Ali, Marits, Per, Sherif, Amir, Winqvist, Ola
• Format: Journal Article
• Language: English
• Published: United States 01.06.2013
• Subjects: Aged; Aged, 80 and over; Amino Acid Sequence; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Base Sequence; Female; Gene Rearrangement, B-Lymphocyte; Humans; Immunoglobulin Heavy Chains - chemistry; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Variable Region - chemistry; Immunoglobulin Variable Region - genetics; Immunologic Memory; Immunophenotyping; Lymph Nodes - immunology; Lymphocyte Activation - immunology; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Male; Middle Aged; Molecular Sequence Data; Neoplasms - immunology; Neoplasms - metabolism; Phenotype; Sequence Alignment; Somatic Hypermutation, Immunoglobulin
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1203279

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 Igλ/Igκ 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.