The re-emergence of the B1 cell compartment: Is this a pre-lymphoma stage?

Authors: Norman Formosa, Christian Saliba, Shawn Baldacchino, David J. Camilleri, Godfrey Grech

Corresponding: Godfrey Grech (godfrey.grech@um.edu.mt)

Keywords: CD5+ B cells, exosomes, CLL, lymphocytosis

Doi: http://dx.medra.org/10.7423/XJENZA.2016.1.02

Issue: Xjenza Online Vol. 4 Iss. 1 - July 2016

Abstract:
Chronic Lymphocytic Leukemia (CLL) are in some cases stereotyped for immunoglobulin variants in different populations, suggesting emergence of B cell subsets following presentation of the same antigen. CLL cells may originate from CD5+ nave cells and from CD5 memory cells. Gene expression studies characterized a common cell of origin of the two clinical categories of CLL; the unmutated aggressive type and the mutated indolent type. The aim of this study was to investigate the presence of CD5 positive B cells in the elderly and their potential stimulation with exosomes derived from tumor cells. The ndings from this study is aimed to create a model to identify instigating carcinomatous factors that may stimulate B1 cells to transform into a CLL-like model. In this study we show that CD19+ cells (B cells) in cord blood have a high expression of CD5. CD19/CD5 staining of blood samples from senior citizens showed the presence of B cells which also express the CD5 marker, though at a lower expression when compared to CLL cells (CD19+/CD5dim B cells). Measurement of clonality using «/ ow cytometry staining show a monoclonal origin of the human CD19+/CD5dimB cells. Monoclonal B cell Lymphocytosis in the elderly is a potential cell compartment that represents the origin of B cell proliferative disorders. The origin of the B cell proliferative disease requires antigen stimulation. A preliminary experiment showed that sorted lymphocytes can be stimulated by exosomes isolated from 2 cancer cells lines, A549 (lung epithelial) and PC3 (prostate cell line). In comparison with phytohaemagglutinin (PHA) and phorbolmyristate acetate (PMA), known lymphocyte stimulators, the exosomes stimulated the proliferation of monocytic-like cells. Further characterization is required to know the origin of these cells. The result shows that one can speculate that exosomes present cancer-derived antigens and stimulate cell proliferation. Further studies are required to evaluate the potential transformation capacity of cancer-derived exosomes. In addition, various cytokines were measured in the sera of senior citizens to investigate a differential release of cytokines in the presence or absence of the CD19+/CD5dim B cells. Cytokines examined were not signicantly different between the 2 groups and further evaluation of cytokine levels is required.

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