Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen

B-cell follicles constitute large reservoirs of infectious HIV/SIV associated to follicular dendritic cells and infecting follicular helper (T-FH) and regulatory (T-FR) T-cells in germinal centers (GCs). Thus, follicular and GC B-cells are persistently exposed to viral antigens. Despite recent development of potent HIV immunogens, numerous questions are still open regarding GC reaction during early HIV/SIV infection. Here, we dissect the dynamics of B- and T-cells in GCs of macaques acutely infected by SIV (Group SIV+) or vaccinated with Tetanus Toxoid (Group TT), a T-dependent model antigen. Systemic inflammation and mobilization of antigen-presenting cells in inguinal lymph nodes and spleen are lower in Group TT than in Group SIV+. Despite spleen GC reaction of higher magnitude in Group SIV+, the development of protective immunity could be limited by abnormal helper functions of T-FH massively polarized into T-FH1-like cells, by inflammation-induced recruitment of fCD8 (either regulatory or cytotoxic) and by low numbers of T-FR limiting T-FH/T-FR competition for high affinity B-cells. Increased GC B-cells apoptosis and accumulation of CD21(lo) memory B-cells, unable to further participate to GC reaction, likely contribute to eliminate SIV-specific B-cells and decrease antibody affinity maturation. Surprisingly, functional GCs and potent TT-specific antibodies develop despite low levels of CXCL13.

Automated summary

The study examined the impact of SIV infection and TT vaccination on the dynamics of B- and T-cells in macaque germinal centers, revealing abnormal helper functions of T-FH cells and reduced numbers of T-FR cells in the SIV infection group, which may limit the development of protective immunity.