title: Mass cytometry analysis shows that a novel memory phenotype B cell is expanded in multiple myeloma.
abstract: It would be very beneficial if the status of cancers could be determined from a blood specimen. However, peripheral blood leukocytes are very heterogeneous between individuals, and thus high-resolution technologies are likely required. We used cytometry by time-of-flight and next-generation sequencing to ask whether a plasma cell cancer (multiple myeloma) and related precancerous states had any consistent effect on the peripheral blood mononuclear cell phenotypes of patients. Analysis of peripheral blood samples from 13 cancer patients, 9 precancer patients, and 9 healthy individuals revealed significant differences in the frequencies of the T-cell, B-cell, and natural killer-cell compartments. Most strikingly, we identified a novel B-cell population that normally accounts for 4.0% ± 0.7% (mean ± SD) of total B cells and is up to 13-fold expanded in multiple myeloma patients with active disease. This population expressed markers previously associated with both memory (CD27(+)) and naïve (CD24(lo)CD38(+)) phenotypes. Single-cell immunoglobulin gene sequencing showed polyclonality, indicating that these cells are not precursors to the myeloma, and somatic mutations, a characteristic of memory cells. SYK, ERK, and p38 phosphorylation responses, and the fact that most of these cells expressed isotypes other than IgM or IgD, confirmed the memory character of this population, defining it as a novel type of memory B cells.
authors.affiliation: Department of Microbiology and Immunology, Stanford University, Stanford, California.
authors.forename: Leo
authors.initials: L
authors.lastname: Hansmann
authors.affiliation: Division of Immunology and Rheumatology, Stanford University, Stanford, California.
authors.forename: Lisa
authors.initials: L
authors.lastname: Blum
authors.affiliation: Division of Immunology and Rheumatology, Stanford University, Stanford, California.
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Ju
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University, Stanford, California.
authors.forename: Michaela
authors.initials: M
authors.lastname: Liedtke
authors.affiliation: Division of Immunology and Rheumatology, Stanford University, Stanford, California.
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.affiliation: Department of Microbiology and Immunology, Stanford University, Stanford, California. Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, California. The Howard Hughes Medical Institute, Stanford University, Stanford, California. mmdavis@stanford.edu.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D049109:Cell Proliferation; D002869:Chromosome Aberrations; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D007156:Immunologic Memory; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D009154:Mutation; D009367:Neoplasm Staging; D010641:Phenotype; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell; D051217:Toll-Like Receptor 9