CD39: an antibody-secreting cell marker and a regulator of B cell response

ALMADA, LAURA; GAZZONI, YAMILA; BECCARIA, CRISTIAN G.; FIOCCA VERNENGO, FACUNDO; BOCCARDO, SANTIAGO; GOROSITO SERRÁN, MELISA; APURWA TRIVEDI; ACOSTA RODRIGUEZ, EVA V.; MONTES, CAROLINA; GAYA, MAURO; GRUPPI, ADRIANA

Congreso; Reunión Anual de la Sociedad Argentina de Inmunología; 2023

Sociedad Argentina de Inmunología

Antibody-secreting cells (ASC) are the only ones able of conferring the organism the ability of protection through immunoglobulin (Ig) release. Antibodies (Abs) are essential components for immunity against pathogens and have different functions depending on its isotype. ASCs can act beyond Abs production; they have heterogeneous functions, extending from dampening the immune system via regulatory mechanisms to antigen presentation and cytokine production. Recently was shown that ASCs hydrolyze extracellular ATP (eATP) to AMP through the ectoenzyme CD39 and generate Adenosine (ADO) which inhibits macrophage function. Yet, whether CD39 and ADO control the magnitude or quality of B cell responses remains unknown.Here, we deeply characterize acute ASC response in T. cruzi experimental infection and further investigated the expression and function of CD39 on B cell compartment in a complete range of experimental models.Through FACS and bulk RNAseq we found that short-lived ASCs, known as plasmablasts (PBs), from spleen and lymph nodes of T. cruzi infected mice have not only different phenotype and genetic expression but also distinct Ab profile, which could be conditioned by the differential distribution on T cell subsets and cytokines in these tissues. Nevertheless, both of them expressed higher levels of CD39 than any other B and T cell populations. Additionally, long lived plasma cells from chronic T. cruzi or influenza virus infected mice had elevated CD39 levels.High expression of CD39 was also observed in ASCs after immunization with red blood cells, infection with S. aureus, P. falciparum or Influenza virus, autoimmune models (Sanroque and FASLpr) and from COVID-19 patients. CD39 on PBs from T. cruzi-infected mice was functional since they had exonuclease activity, evidenced by a decrease in eATP levels in PBs-culture supernatant in comparison to naïve B cell-culture medium. This activity was partially reversed by ARL, a CD39 inhibitor, and reduced in PB from infected CD39KO mice.To assess the role of CD39 in B cell responses, we infected CD39KO mice with T. cruzi. We found that CD39 was dispensable for PB differentiation, but ASC from T. cruzi infected CD39KO mice developed an altered profile of Ig compared to WT mice. Yet, chimera mice lacking CD39 only on B cell compartment and infected with Influenza exhibited an increased frequency of GCs when compared to controls, suggesting that CD39+PBs may limit GC reaction. Then, we evaluated whether this phenomenon was mediated by ADO. We found that ADO administration significantly impaired GC reaction. These results go in line with increased ADO receptor (Adora2) expression observed by bulk RNAseq upon B cell activation.Our findings highlight CD39 as ASC marker with an important role in shaping the profile and magnitude of Ab response. Also, we unveiled an unknown regulatory axis between PBs and GCs, where early formation of CD39+PBs modulates eATP and regulate the GC expansion.