Generation of polyclonal plasmablasts from peripheral blood B cells: a normal counterpart of malignant plasmablasts

Abstract

A new way to identify tumor-specific genes is to compare gene expression profiles between malignant cells and their autologous normal counterparts. In patients with multiple myeloma, a major plasma cell disorder, normal plasma cells are not easily attainable in vivo. We report here that in vitro differentiation of peripheral blood B lymphocytes, purified from healthy donors and from patients with multiple myeloma, makes it possible to obtain a homogeneous population of normal plasmablastic cells. These cells were identified by their morphology, phenotype, production of polyclonal immunoglobulins, and expression of major transcription factors involved in B-cell differentiation. Oligonucleotide microarray analysis shows that these polyclonal plasmablastic cells have a gene expression pattern close to that of normal bone marrow–derived plasma cells. Detailed analysis of genes statistically differentially expressed between normal and tumor plasma cells allows the identification of myeloma-specific genes, including oncogenes and genes coding for tumor antigens. These data should help to disclose the molecular mechanisms of myeloma pathogenesis and to define new therapeutic targets in this still fatal malignancy. In addition, the comparison of gene expression between plasmablastic cells and B cells provides a new and powerful tool to identify genes specifically involved in normal plasma cell differentiation.

Marginal zone B cell lymphomas with extensive plasmacytic differentiation are neoplasms of precursor plasma cells

“…Intracellular light chain staining revealed the plasmacytic cells were polyclonal. The phenotype was similar to that previously reported for the plasmacytic cells in RP (14,(16)(17)(18)(19)(20).…”

“…The clonal cells in P-MZL appeared plasmacytic based on the composite phenotype. To determine the relationship of these cells with other plasmacytic processes we compared the phenotype of P-MZL with PCM and with the precursor plasma cells present in RP (14,(16)(17)(18)(19). Sixteen cases of PCM were evaluated.…”

“…Reactive plasmacytoses (RP) in patients with autoimmune or infectious diseases contain plasmacytic cells that are felt to be precursors to mature marrow plasma cells (14)(15)(16)(17). A large portion of these cells are highly proliferative and are considered plasmablasts (14)(15)(16)(17)(18)(19)(20). The cells can be distinguished from more mature plasma cells by lack of or partial expression of CD138, stronger expression of CD45 and HLA-DR, and expression of CD95 and chemokine receptors (14,(16)(17)(18)(19)(20).…”

“…A large portion of these cells are highly proliferative and are considered plasmablasts (14)(15)(16)(17)(18)(19)(20). The cells can be distinguished from more mature plasma cells by lack of or partial expression of CD138, stronger expression of CD45 and HLA-DR, and expression of CD95 and chemokine receptors (14,(16)(17)(18)(19)(20). Tumors of plasmablasts include plasmablastic lymphomas, a rare aggressive tumor with large cell morphology, ALKþ DLBCL, and DLBCL associated with Castleman's disease and HHV-8 infection (1,(21)(22)(23).…”

Inhibition of cyclooxygenase‐2 impairs the expression of essential plasma cell transcription factors and human B‐lymphocyte differentiation

“…[17][18][19] Plasma cell precursors have been defined by numerous investigators as CD38 + antibody-secreting cells. [17][18][19] Arce et al 17 demonstrated that CD38 ) IgG-secreting cells generated from blood-derived B cells gave rise to CD38 + antibody-secreting plasma cell precursors. We observed no change in the frequency of CD38 ) antibody-secreting cells after treatment with Cox-2 inhibitors.…”