RESUMEN
The comprehension of unconventional immune functions of tonsillar B cells, their role in tolerance induction and protective immune responses, is crucial to unveil the dynamic interactions of the upper aero digestive tract with polymicrobial commensal flora and pathogens, in health and disease. Here, we describe the kinetics of IL10 intracellular expression and compare it with that of cytokines known to be produced by tonsillar B cells. Additionally, we detected a relevant proportion of IL17-expressing tonsillar B cells, which has not previously been reported. We immunophenotyped tonsillar IL10-expressing B cells (B10) and observed IL10 production in activated B cells at every developmental stage. Finally, we identified a relationship between decreased B10 percentages, increased proportion of the germinal centre (GC) population and hypertrophied tonsils (HT). Our findings provide greater insight into the role of B10 in GC reactions and characterized their involvement in the pathogenesis of tonsillar dysfunction.
Asunto(s)
Linfocitos B/inmunología , Linfocitos B/metabolismo , Interleucina-10/biosíntesis , Tonsila Palatina/citología , Tonsila Palatina/inmunología , Biomarcadores , Biología Computacional/métodos , Centro Germinal/inmunología , Humanos , Hipertrofia , Inmunofenotipificación , Tonsila Palatina/metabolismo , Tonsilitis/inmunología , Tonsilitis/metabolismo , Tonsilitis/patologíaRESUMEN
The expression of N-glycolyl-monosialodihexosyl-ganglioside (NGcGM3) in humans is restricted to cancer cells; therefore, it is a tumor antigen. There are measurable quantities of circulating anti-NGcGM3 antibodies (aNGcGM3 Abs) in human serum. Interestingly, some people have circulating Ag-specific immunoglobulins G (IgGs) that are capable of complement mediated cytotoxicity against NGcGM3 positive cells, which is relevant for tumor surveillance. In light of the chemical nature of Ag, we postulated it as a candidate ligand for CD1d. Furthermore, we hypothesize that the immune mechanism involved in the generation of these Abs entails cross talk between B lymphocytes (Bc) and invariant natural killer T cells (iNKT). Combining cellular techniques, such as flow cytometry and biochemical assays, we demonstrated that CD1d binds to NGcGM3 and that human Bc present NGcGM3 in a CD1d context according to two alternative strategies. We also showed that paraformaldehyde treatment of cells expressing CD1d affects the presentation. Finally, by co-culturing primary human Bc with iNKT and measuring Ki-67 expression, we detected a reproducible increment in the proliferation of the iNKT population when Ag was on the medium. Our findings identify a novel, endogenous, human CD1d ligand, which is sufficiently competent to stimulate iNKT. We postulate that CD1d-restricted Bc presentation of NGcGM3 drives effective iNKT activation, an immunological mechanism that has not been previously described for humans, which may contribute to understanding aNGcGM3 occurrence.