| Summary: | B-cell follicles constitute large reservoirs of infectious HIV/SIV associated to follicular dendritic cells and infecting follicular helper (T<sub>FH</sub>) and regulatory (T<sub>FR</sub>) 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<sup>+</sup>) 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<sup>+</sup>. Despite spleen GC reaction of higher magnitude in Group SIV<sup>+,</sup> the development of protective immunity could be limited by abnormal helper functions of T<sub>FH</sub> massively polarized into T<sub>FH1</sub>-like cells, by inflammation-induced recruitment of fCD8 (either regulatory or cytotoxic) and by low numbers of T<sub>FR</sub> limiting T<sub>FH</sub>/T<sub>FR</sub> competition for high affinity B-cells. Increased GC B-cells apoptosis and accumulation of CD21<sup>lo</sup> 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.
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