Distinct profiles and antibody production by splenic and lymph node antibody-secreting cells in Trypanosoma cruzi infection

Evidence from bone marrow and intestinal lamina propria studies indicates that antibody-secreting cell (ASC) characteristics are shaped by the local microenvironment; yet whether secondary lymphoid organs harbor distinct ASC populations during infection remains unclear. Here, we investigated plasmablasts (PB) from the spleen and inguinal lymph nodes (LN) in acute Trypanosoma cruzi infection. Although PB from both tissues expressed canonical ASC markers, they displayed distinct transcriptional, phenotypic, and functional profiles. Splenic PB upregulated genes and proteins associated with inflammation, immunomodulation, and B-cell interactions. Activated and naive B cells also exhibited tissue-specific transcriptional programs, suggesting that local cues influence B-cell differentiation. Consistent with these differences, spleens from infected mice contained more T follicular helper cells, whereas LN were enriched in regulatory T cells. High-dimensional flow cytometry identified multiple PB subsets differentially represented between tissues. Functionally, splenic PB secreted higher levels of IgM, IgA, and IgG, including both parasite-specific and autoreactive antibodies. In contrast, LN PB preferentially produced IgG against peptide 72 of the shed acute-phase antigen (SAPA), despite lower overall T. cruzi-specific antibody production. These findings demonstrate that secondary lymphoid organs harbor distinct PB populations adapted to their local microenvironments during acute infection