title: In multiple myeloma clonotypic CD38- /CD19+ / CD27+ memory B cells recirculate through bone marrow, peripheral blood and lymph nodes.
abstract: It is believed that myeloma cells are derived from a germinal center (GC) or post GC B cell. The GC B cell can differentiate into both a memory B cell and a plasma cell (PC). In this study, we investigated the recirculating potential of memory B cells clonally related to the myeloma PC (termed clonotypic). The V(H)DJ(H) immunoglobulin gene rearrangement of the myeloma clone was identified for 10 myeloma patients and allele-specific oligonucleotides (ASO) IgH RT-PCR assays were designed for each patient. Memory B cells (CD38- /CD19+ /CD27+) and their subsets defined by the monoclonal antibodies CD62L, CCR6, CXCR4, CXCR5, CCR7 were flow-sorted as single cells and analyzed by ASO RT-PCR analysis. In addition, aspirated peripheral lymph nodes (PLN) of 7 myeloma patients in complete or partial remission were analyzed for the presence of clonotypic cells. Circulating clonotypic memory B cells were identified in PBMNC of 7/10 patients and both CD62L positive and negative clonotypic memory B cells were identified. Furthermore, comparable frequencies of clonotypic cells were found in the CCR6 +/- and CXCR4 +/- memory B cell subsets, whereas all clonotypic memory and later stage B cells were CXCR5 positive. In accordance with their immunophenotype, clonotypic memory B-cells were identified in peripheral blood, bone marrow and PLNs. Clonotypic memory B-cells were present in the majority of myeloma patients and seem to have the same diverse recirculating/homing capacity as normal memory B cells.
authors.affiliation: Department of Hematology L 54P4, University of Copenhagen, 2730 Herlev, Denmark. thra@herlevhosp.kbhamt.dk
authors.forename: Thomas
authors.initials: T
authors.lastname: Rasmussen
authors.forename: Marianne
authors.initials: M
authors.lastname: Lodahl
authors.forename: Søren
authors.initials: S
authors.lastname: Hancke
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Johnsen
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000032:analysis; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000032:analysis; D018941:Antigens, CD19 / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology*; D002465:Cell Movement; D002999:Clone Cells / Q000473:pathology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D019041:L-Selectin / Q000032:analysis; D008198:Lymph Nodes / Q000473:pathology*; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins; D009101:Multiple Myeloma / Q000097:blood / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis; D054380:Receptors, CXCR5; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000032:analysis; D011991:Receptors, Virus / Q000032:analysis; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
chemical_list: D015703:Antigens, CD; D018941:Antigens, CD19; C095085:CXCR5 protein, human; C106330:CXCR6 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D019718:Receptors, CXCR4; D054380:Receptors, CXCR5; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019041:L-Selectin; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1