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: