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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 dev...

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Detalles Bibliográficos
Autores principales: Trovato, Maria, Ibrahim, Hany M., Isnard, Stephane, Le Grand, Roger, Bosquet, Nathalie, Borhis, Gwenoline, Richard, Yolande
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916050/
https://www.ncbi.nlm.nih.gov/pubmed/33572146
http://dx.doi.org/10.3390/v13020263
Descripción
Sumario: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.