B cells from Patients with Rheumatoid Arthritis Show Conserved CD39-Mediated Regulatory Function and increased CD39 Expression After Positive Response to Therapy.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive joint destruction associated with increased pro-inflammatory mediators. In inflammatory microenvironments, exogenous ATP (eATP) is hydrolyzed to adenosine, which exerts immunosuppressive effects, by the consecutive action of the ectonucleotidases CD39 and CD73. Mature B cells constitutively express both ectonucleotidases, converting these cells to potential suppressors. Here, we assessed CD39 and CD73 expression on B cells from treated or untreated patients with RA. Neither the frequency of CD73+CD39+ and CD73-CD39+ B cell subsets nor the levels of CD73 and CD39 expression on B cells from untreated or treated RA patients showed significant changes in comparison to healthy controls (HC). CpG+IL-2-stimulated B cells from HC or untreated RA patients increased their CD39 expression, and suppressed CD4+ and CD8+ T cell proliferation and intracellular TNF-production. A CD39 inhibitor significantly restored proliferation and TNF-producing capacity in CD4+ T cells, but not in CD8+ T cells, from HC and untreated RA patients, indicating that B cells from untreated RA patients conserved CD39-mediated regulatory function. Good responder patients to therapy (R-RA) exhibited an increased CD39 but not CD73 expression on B cells after treatment, while most of the non-responder (NR) patients showed a reduction in ectoenzyme expression. The positive changes of CD39 expression on B cells exhibited a negative correlation with disease activity and rheumatoid factor levels. Our results suggest modulating the ectoenzymes/ADO pathway as a potential therapy target for improving the course of RA.

Echinococcus granulosus glycoconjugates induce peritoneal B cell differentiation into antibody-secreting cells and cytokine production.

Helminth parasite infections are associated with predominant Th2-type cytokine responses, and parasite glycoconjugates have been recognized as partially responsible for such immune bias. It has been proved that Echinococcus granulosus evokes a Th2-type cytokine pattern characterized by a high production of IL-4, IL-5, IL-6 and IL-10, and no or mild IFN-γ levels in animal models and in patients with cystic echinococcosis, respectively. Here, we show that E4(+) (a glycoconjugate-enriched fraction from E. granulosus protoscolex) stimulated the secretion of a high concentration of IL-6, followed by IL-10 and TNF-α by normal peritoneal B cells. We determined that E4(+) bound to the surface of peritoneal B cells and induced their activation and, also, triggered the differentiation of peritoneal B cells into IgM-, IgG2b- and IgG3-secreting cells in a T-independent way. Interestingly, the IgM released by E4(+) -stimulated peritoneal B cells from normal mice recognized protoscolex antigens. Results showed that, after the encounter with antigens from E. granulosus protoscolex, peritoneal B cells are a source of Th2-type cytokines and polyclonal antibodies, some of which recognize parasite antigens, suggesting that peritoneal B cells can condition the outcome of the infection.

Trypanosoma cruzi infection beats the B-cell compartment favouring parasite establishment: can we strike first?

Trypanosoma cruzi, the causative agent of Chagas' disease, may sabotage humoral response by affecting B cells at the different stages of its development. The present review highlights the contributions of our laboratory in understanding how T. cruzi hinders B-cell generation and B-cell expansion limiting host defence and favouring its chronic establishment. We discuss how homoeostatic mechanisms can be triggered to control exacerbated B-cell proliferation that favour T. cruzi infection by eliminating parasite-specific B cells. Specific targeting of evasion mechanisms displayed in T. cruzi infection, as in vivo Fas/FasL blockade or Gal-3 expression inhibition, allowed us to modulate B-cell responses enhancing the anti-parasite humoral immune response. A comprehensive understanding of the biology of the B cell in health and disease is strictly required to devise immunointervention strategies aimed at enhancing protective immune responses during infections.