title: Circulating clonotypic B cells in multiple myeloma and monoclonal gammopathy of undetermined significance.
abstract: The B-cell compartment in which multiple myeloma stem cells reside remains unclear. We investigated the potential presence of mature, surface-membrane immunoglobulin-positive B lymphocytes clonally related to the tumor bone marrow plasma cells among different subsets of peripheral blood B cells from ten patients (7 with multiple myeloma and 3 with monoclonal gammopathies of undetermined significance). The presence of clonotypic immunoglobulin heavy chain gene rearrangements was determined in multiple highly-purified fractions of peripheral blood B-lymphocytes including surface-membrane IgM(+) CD27(-) naïve B-lymphocytes, plus surface-membrane IgG(+), IgA(+) and IgM(+) memory CD27(+) B cells, and normal circulating plasma cells, in addition to (mono)clonal plasma cells, by a highly-specific and sensitive allele-specific oligonucleotide polymerase chain reaction directed to the CDR3 sequence of the rearranged IGH gene of tumor plasma cells from individual patients. Our results showed systematic absence of clonotypic rearrangements in all the different B-cell subsets analyzed, including M-component isotype-matched memory B-lymphocytes, at frequencies <0.03 cells/μL (range: 0.0003-0.08 cells/μL); the only exception were the myeloma plasma cells detected and purified from the peripheral blood of four of the seven myeloma patients. These results indicate that circulating B cells from patients with multiple myeloma and monoclonal gammopathies of undetermined significance are usually devoid of clonotypic B cells while the presence of immunophenotypically aberrant myeloma plasma cells in peripheral blood of myeloma patients is a relatively frequent finding.
authors.affiliation: orfao@usal.es.
authors.forename: Leandro S
authors.initials: LS
authors.lastname: Thiago
authors.forename: Martin
authors.initials: M
authors.lastname: Perez-Andres
authors.forename: Ana
authors.initials: A
authors.lastname: Balanzategui
authors.forename: Maria E
authors.initials: ME
authors.lastname: Sarasquete
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.forename: Maria
authors.initials: M
authors.lastname: Jara-Acevedo
authors.forename: Paloma
authors.initials: P
authors.lastname: Barcena
authors.forename: Maria Luz
authors.initials: ML
authors.lastname: Sanchez
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.forename: Jesus F
authors.initials: JF
authors.lastname: San Miguel
authors.forename: Ramón
authors.initials: R
authors.lastname: Garcia-Sanz
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D016175:B-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002999:Clone Cells / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D018655:Lymphocyte Count; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000378:metabolism* / Q000473:pathology*; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology*; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism
chemical_list: D011947:Receptors, Antigen, B-Cell