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The effect of Thalassophryne nattereri venom plus IL-17A as inducing factors in the extrafollicular Ig class switching

Grant number: 13/12622-6
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2013
Effective date (End): December 31, 2013
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Carla Lima da Silva
Grantee:Vanessa Alcantara Garcia
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The B1 cells are found predominantly in the peritoneal and pleural cavities and are largely responsible for the production of low-affinity IgM, poly-reactive. Follicular B2 cells after follicular dendritic cell (fDC) and follicular T cell (FTH) undergo a series of processes in the germinal center (GC) where occurs immunoglobulin class switching and affinity maturation of antibodies provided by somatic mutations in the variable region of the CDR portion. This process will form the memory compartment composed of memory B cells (Bmem) and ASC (long-living antibody-secreting cells) that leave the germinal center of the follicle toward the inflamed tissues containing the pathogen, recirculate through the blood or lymph and fix for long periods in the bone marrow. Recent data show that both innate B cell populations (B1 and B2) are able to differentiate and form the compartment of memory B cells using the classical route in the GC and the extrafollicular route. In the extrafollicular route, innate B1 cells that did not enter the GC will not suffer a somatic mutation in immunoglobulin genes and cells are short-lived. Unpublished data from our group reveal that during the hierarchical process of differentiation, CD19 positive B lymphocytes purified from cell suspensions (peritoneal, spleen, and bone marrow) 48 d after immunization with venom possess the ability to differentiate in vitro into ASC with CD138+IgG+ phenotype. And also, we observed that CD19 positive B lymphocytes purified from the peritoneum (probably the subpopulation B1) of control animals differentiate in vitro after combined stimulation with venom plus IL-17A into cells with negative expression of CD138 but positive for intracellular IgG. These data reinforce the idea that recombination and class switching from IgM to IgG, IgA or IgE may also occur outside of CG, unlike the prevailing view that only the specialized splenic environment GC coordinates affinity maturation and somatic hypermutation of Abs. According to these data, the aim of this project is to determine the role of the combined effect of the venom + IL-17A in the induction of Ig class switching in ASC derived from different subtypes of innate B cells (B1a or B2) of the peritoneum.(AU)

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