Sonia Néron, Ph. D.

Research Scientist, Cellular Engineering Ph.D. Biochemistry, Université Laval, 1995 Adjunct Professor, Department of Biochemistry and Microbiology, Université Laval Tel.: 418 780-4362, ext. 3260 Sonia.Neron@hema-quebec.qc.ca

Research Interests:

• Human B-lymphocyte physiology, modulation of the immune response

Current Projects:

• Control of In Vitro Expansion and Differentiation of B Lymphocytes
• Effects of Therapeutic Immunoglobulin (IVIg) on B-Lymphocyte Function in the Treatment of Autoimmune Diseases

Therapeutic immunoglobulin or intravenous immunoglobulin (IVIg) is prepared from plasma pooled from thousands of donors. IVIg is used in the treatment of primary and secondary immunodeficiencies, and is also a valuable treatment option for several autoimmune and inflammatory diseases. For the past several years, IVIg utilization has been on the rise; indeed, new clinical indications for IVIg are constantly being reported in the scientific literature. Although the worldwide IVIg supply satisfies current needs, the development of new technologies allowing the laboratory production of IVIg substitutes on an industrial scale could secure the long-term supply of this plasma derivative.

CD154-expressing L4.5 feeder cells stained with fluorescent markers. In blue: nuclei; in red: actin; in green: mitochondria. Magnification: 1,000

Control of In Vitro Expansion and Differentiation of B Lymphocytes

Immunoglobulins G (IgG), which make up more than 98% of IVIg, are produced by human B lymphocytes. IgG-secreting B lymphocytes are the main contributors of the humoral secondary immune response; hence, they are referred to as “memory” B lymphocytes. These cells can be isolated from either blood samples or whole blood leukocyte reduction filters. All human B lymphocytes express CD40 on their surface, allowing for the in vitro stimulation by exposing cells to CD154 (the CD40 ligand). The in vitro culture in the presence of the appropriate cytokine cocktail and CD154-expressing L4.5 cells leads to the proliferation and differentiation of B lymphocytes. Dr. Néron and her team have observed that naïve and memory B lymphocytes differentially respond to the in vitro CD40 stimulation. This result allowed to define the optimal CD40-CD154 interaction for memory B cell expansion and in particular IgG+ cells. Current work is focused on the cellular and molecular mechanisms involved in the differentiation of naïve and memory B lymphocytes in response to CD40 stimulation. The long-term goal of this project aims at developing a culture system for the laboratory preparation of human immunoglobulins for therapeutic use.

Effects of Therapeutic Immunoglobulin (IVIg) on B-Lymphocyte Function in the Treatment of Autoimmune Diseases

One of the strategies aimed at reducing the demand for IVIg is to elucidate its mechanism of action and to identify its immune targets. In this area of investigation, Dr. Néron’s work has demonstrated that IVIg inhibit proliferation while simultaneously inducing differentiation of human B lymphocytes into IgG-secreting cells and activating intracellular signal transduction pathways related to the kinase phosphorylation cascade. Her team is currently testing the hypothesis suggesting that IVIg could exert direct effects on a specific B-lymphocyte subpopulation through a membrane receptor that triggers a signalling cascade responsible for differentiation. Dr. Néron and her team are assessing the relevance of this IVIg-induced immunomodulation of B lymphocytes to immune system homeostasis, and the possible involvement of cell-cell communication with T lymphocytes. Her team is currently focusing on the cellular and molecular aspects of the mechanisms of action of IVIg on B and T lymphocytes from healthy individuals or from patients suffering from systemic lupus erythematosus, using the CD40-CD154 in vitro stimulation model.

Recent Publications:

• Néron S, Roy A, Dumont N. (2012). Large-scale in vitro expansion of polyclonal human switched-memory B lymphocytes. PLoS One (PLoS One) 7 (12): e51946.
• Néron S., Roy, A. (2012). Overview of IgG-reactivity in therapeutic immunoglobulins revealed by protein array analysis.Biochemistry & Analytical Biochemistry (Biochemistry & Analytical Biochemistry) S8: 001.
• Nadeau PJ, Roy A, Gervais St-Amour C, Marcotte MÈ, Dussault N, Néron S. (2012). Modulation of CD40-activated B lymphocytes by N-acetylcysteine involves decreased phosphorylation of STAT3. Mol Immunol (Molecular Immunology) 49 (04): 582-592. 
• Dussault N, Dumont N, Néron S. (2011). Modulation of human B lymphocyte differentiation by therapeutic immunoglobulins: from protein to mRNA levels. Open Journal of Immunology (Open Journal of Immunology) 1 (03): 65-73.
• Néron S, Côté G, Dumont N, Roy A, Fecteau JF, McNeil MÈ. (2011). Contribution of CD40-activated naïve B lymphocytes in the modulation of CD27+ memory B cell growth and differentiation. In : Advances in Medicine and Biology, vol. 25. Bernhardt, LV, Collection Editor (Hauppauge, NY, Nova Science Publishers, Inc., 306 pp.): 143-167.
• Néron S, Roy A, Dumont N, Dussault N. (2011). Effective in vitro expansion of CD40-activated human B lymphocytes in a defined bovine protein-free medium. J Immunol Methods (Journal of Immunological Methods) 371 (1-2): 61-69
• Néron S, Nadeau PJ, Darveau A, Leblanc JF. (2011). Tuning of CD40–CD154 Interactions in Human B-Lymphocyte Activation: A Broad Array of In Vitro Models for a Complex In Vivo Situation. Arch Immunol Ther Exp (Warsz) (Archivum Immunologiae et Therapiae Experimentalis) 59 (1): 25-40.
• Néron S, Boire G, Dussault N, Racine C, de Brum-Fernandes AJ, Côté S, Jacques A. (2009). CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro. Arch Immunol Ther Exp (Warsz) 57 (6): 447-458.
• Ducas É, Dussault N, Roy A, Dumont N, Néron S. (2009). Estimation of the number of CD154 molecules in membrane extracts used as a source of CD40 stimulation of human B lymphocytes. J Immunol Methods (Journal of Immunological Methods) 344 (2): 133-137.
• Cayer MP, Proulx M, Ma XZ, Sakac D, Giguère JF, Drouin M, Néron S, Branch DR, Jung D. (2009). c-Src tyrosine kinase co-associates with and phosphorylates signal transducer and activator of transcription 5b which mediates the proliferation of normal human B lymphocytes. Clin Exp Immunol (Clinical & Experimental Immunology) 156 (3): 419-427.
• Fecteau JF, Roy A, Néron S. (2009). Peripheral blood CD27+ IgG+ B cells rapidly proliferate and differentiate into immunoglobulin-secreting cells after exposure to low CD154 interaction. Immunology (Immunology) 128 (1Suppl): e353-e365.
• Dussault N, Ducas É, Racine C, Jacques A, Paré I, Côté S, Néron S. (2008). Immunomodulation of human B cells following treatment with intravenous immu-noglobulins involves increased phosphorylation of extracellular signal-related kinases 1 and 2. Int Immunol (International Immunology) 20 (11): 1369-1379.
• Néron S, Thibault L, Dussault N, Côté G, Ducas É, Pineault N, Roy A. (2007). Characterization of mononuclear cells remaining in the leukoreduction system chambers of apheresis instruments after routine platelet collection: a new source of viable human blood cells. Transfusion (Transfusion) 47 (06): 1042-1049.
• Dussault N, Simard C, Néron S, Côté, S. (2007). Human B lymphocytes and non-Hodgkin's lymphoma cells become polyploid in response to the protein kinase inhibitor SU6656. Blood Cells Mol Dis (Blood Cells, Molecules, and Diseases) 39 (1): 130-134.
• Fecteau JF, Côte G, Néron S. (2006). A new memory CD27-IgG+ B cell population in peripheral blood expressing VH genes with low frequency of somatic mutation. J Immunol (Journal of Immunology) 177 (06): 3728-3736.
• Néron S, Dussault N, Racine C. (2006). Whole-blood leukoreduction filters are a source for cryopreserved cells for phenotypic and functional investigations on peripheral blood lymphocytes. Transfusion (Transfusion) 46 (04): 537-544.
• Néron S, Suck G, Ma XZ, Sakac D, Roy A, Katsman Y, Dussault N, Racine C, Branch DR. (2006). B cell proliferation following CD40 stimulation results in the expression and activation of Src protein tyrosine kinase. Int Immunol (International Immunology) 18 (02): 375-387.
• Néron S, Racine C, Roy A, Guérin M. (2005). Differential responses of human B-lymphocyte subpopulations to graded levels of CD40-CD154 interaction. Immunology (Immunology) 116 (4): 454-463.
• Jung D, Néron S, Drouin M, Jacques A. (2005). Efficient gene transfer into normal human B lymphocytes with the chimeric adenoviral vector AD5/F35. J Immunol Methods (Journal of Immunological Methods) 304 (1-2): 78-87.
• Lemieux R, Bazin R, Néron S. (2005). Therapeutic intravenous immunoglobulins. Mol Immunol (Molecular Immunology) 42 (07): 839-848.
• Branch DR, Ma XZ, Sakac D, Roy A, Néron S. (2004). pp60c-src Protein Tyrosine Kinase Expression in Human B Lymphocytes. Dans Immunology 2004. Collection of Free Papers Presented at the 12th International Congress of Immunology and 4th Annual Conference of FOCIS (Montréal, Canada, 18 au 23 juillet 2004). Monduzzi, éditeur. Medimond Srl, Bologne, Italie, pp. 129-134.
• Fecteau JF, Néron S. Characterization of Naïve and Memory B Cell Differentiation toward Plasma Cells Following Low CD40 Stimulation. Dans Immunology 2004. Collection of Free Papers Presented at the 12th International Congress of Immunology and 4th Annual Conference of FOCIS (Montréal, Canada, 18 au 23 juillet 2004). Monduzzi, éditeur. Medimond Srl, Bologne, Italie, pp. 303-307.
• Fecteau JF, Néron S. (2003). CD40 stimulation of human peripheral B lymphocytes: distinct response from naive and memory cells. J Immunol (Journal of Immunology) 171 (09): 4621-4629.
• de Grandmont MJ, Racine C, Roy A, Lemieux R, Néron S. (2003). Intravenous immunoglobulins induce the in vitro differentiation of human B lymphocytes and the secretion of IgG. Blood (Blood) 101 (08): 3065-3073.
• Roy A, Krzykwa E, Lemieux R, Néron S. (2001) Increased efficiency of γ-irradiated versus mitomycin C-treated feeder cells for the expansion of normal human cells in long-term cultures. J Hematotherapy Stem Cell Res (Journal of Hematotherapy & Stem Cell Research) 10 (06): 873-880.
• Jung D, Néron S, Lemieux R, Roy A, Richard M. (2001). Telomere-independent reduction of human B lymphocyte proliferation during long-term culture. Immunol Invest (Immunology Investigations) 30 (2): 157-168.