Escalation of Germinal Center Responses in Chronic Litomosoides sigmodontis Filarial Infection

Abstract

T follicular helper (T_FH) cells are the primary CD4⁺ T helper cell subset providing help to B cells for efficient antibody responses in vaccination, allergy, autoimmunity, and infectious diseases. Despite their critical involvement in immunity, T_FH cells' specific role in filarial infections remains unclear. Using the rodent filarial model Litomosoides sigmodontis, we examined T_FH and germinal center (GC) B cell responses in lung-draining mediastinal lymph nodes (medLNs) over a 110-day infection period in naive and infected wildtype (WT) BALB/c mice, as well as eosinophil-deficient dblGATA mice, using flow cytometry and ELISA. We observed robust and prolonged T_FH and GC B cell responses in medLNs of infected BALB/c mice, along with enduring IgG1 antibody responses next to a persistent systemic humoral immune response. We further provide evidence of dysregulated T_FH/T follicular regulatory (T_FR) cell ratios in medLNs. Finally, elevated T_FH cell frequencies in medLNs of dblGATA mice reaffirm the significant role of eosinophils during chronic infection. In conclusion, our findings provide novel insights into population changes of T_FH and GC B cells during filarial infection.

Keywords: B cell; Litomosoides sigmodontis; TFH cell; TFR cell; germinal center.