Characterization of extrafollicular plasmablast response in Trypanosoma cruzi infection

ALMADA L.; GAZZONI Y.; FIOCCA VERNENGO F.; BECCARIA CG.; BOCCARDO S.; GOROSITO SERRAN M.; BOSSIO S.; MUCCI J.; MONTES CL.; ACOSTA-RODRIGUEZ EV; GRUPPI A

Buenos Aires

Congreso; Reunión Anual de Sociedades de Biociencias - SAIC. SAI. SAFIS. 2020; 2020

SAIC. SAI. SAFIS.

B cells are the unique population able to differentiate into antibody-secreting-cells (ASC). The Germinal Center reaction-GC- andthe extrafollicular-EF- response generate different types of ASCwhich 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 ofEF-ASC (B220intCD138+Blimp-1+, Plasmablasts/PB) characterizedby high expression of PD-L1 and CD39, present in murine infectionmodels but not in autoimmunity or immunizations. These PB havethe 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 phenotypeof 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 byFACS at different days post infection (dpi). The 99% of splenic PBexpressed high levels of PD-L1 and CD39 until day 23pi and this frequencywas significantly reduced from day 28pi (p<0.005). Only the15% 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, CD86and Ki-67 and produced IL-21, IL-6 and IL-10, probably conditioningT-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 PBresponse since infected Bcl-6flo/floCD23Cre mice did not exhibit thisASC population. The CXCR5negTfh-like population could be locatedin the EF-area and could be interacting with PB, either collaboratingwith ASC or being regulated by them.