Abstract
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.