CHARACTERIZATION OF EXTRAFOLLICULAR PLASMABLAST RESPONSE IN TRYPANOSOMA CRUZI INFECTION

ALMADA, LAURA; GAZZONI, YAMILA; FIOCCA VERNENGO, FACUNDO; BECCARIA, CRISTIAN G.; BOCCARDO, SANTIAGO; GOROSITO SERRÁN, MELISA; BOSSIO, SABRINA; MUCCI, JUAN; MONTES, CAROLINA L.; ACOSTA RODRÍGUEZ, EVA V.; GRUPPI, ADRIANA

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

SOCIEDAD ARGENTINA DE INMUNOLOGÍA

B cells are the unique population able to differentiate into antibody-secreting-cells (ASC). The Germinal Center reaction-GC- and the extrafollicular-EF- response generate different types of ASC which provide long- and short-term humoral immunity against infections, respectively. The participation of follicular T helper cells -Tfh-, is key in these processes. In our lab, we identified a population of EF-ASC (B220intCD138+Blimp-1+, Plasmablasts/PB) characterized by high expression of PD-L1 and CD39, present in murine infection models but not in autoimmunity or immunizations. These PB have the capability to modulate T-cell response, since chimera modelslacking PD-L1hiPB have an increase in TNF-IFNγ-producing PD-1+CD4+ Tcells. The aim of our work is to characterize the phenotype of regulatory PB and the mediators involved in the PB-Tcell interactions. Therefore, B6 mice were infected with T. cruzi and splenic, lymph node and bone marrow (BM) lymphocytes were evaluated by FACS at different days post infection (dpi). The 99% of splenic PB expressed high levels of PD-L1 and CD39 until day 23pi and this frequency was significantly reduced from day 28pi (p<0.005). Only the 15% of BM-ASC from mice in the chronic phase of infection (130dpi) expressed high levels of PD-L1 and CD39. Splenic PD-L1hiCD- 39hi PB also expressed high levels of CXCR4, MHCII, CD80, CD86 and Ki-67 and produced IL-21, IL-6 and IL-10, probably conditioning T-helper response. In addition, we found CXCR5+ and CXCR5negPD1+ICOS+Bcl-6+CD4+Tcell populations in spleen of infected mice, which produce TNF, IFNγ, IL-4, IL-6, IL-21, probably sustaining PB response since infected Bcl-6flo/floCD23Cre mice did not exhibit this ASC population. The CXCR5negTfh-like population could be located in the EF-area and could be interacting with PB, either collaborating with ASC or being regulated by them.