In Multiple Myeloma Clonotypic CD38 − /CD19 + /CD27 +  Memory B Cells Recirculate Through Bone Marrow, Peripheral Blood and Lymph Nodes

T Rasmussen, M Lodahl, S Hancke… - Leukemia & …, 2004 - Taylor & Francis
T Rasmussen, M Lodahl, S Hancke, HE Johnsen
Leukemia & lymphoma, 2004Taylor & Francis
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 VHDJH 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 …
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 VHDJH 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 7/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+/7 and CXCR4+/7 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.
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