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<sub>FH</sub>) and regulatory (T<sub>FR</sub>) T-cells in germinal centers (GCs). Thus, follicular and GC B-cells are persistently exp...
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MDPI AG
2021-02-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/2/263 |
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| author | Maria Trovato Hany M. Ibrahim Stephane Isnard Roger Le Grand Nathalie Bosquet Gwenoline Borhis Yolande Richard |
| author_facet | Maria Trovato Hany M. Ibrahim Stephane Isnard Roger Le Grand Nathalie Bosquet Gwenoline Borhis Yolande Richard |
| author_sort | Maria Trovato |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T05:01:12Z |
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| id | doaj.art-7a9354c269034c8f830c4751c05950f9 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T05:01:12Z |
| publishDate | 2021-02-01 |
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| series | Viruses |
| spelling | doaj.art-7a9354c269034c8f830c4751c05950f92023-12-03T12:59:21ZengMDPI AGViruses1999-49152021-02-0113226310.3390/v13020263Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model AntigenMaria Trovato0Hany M. Ibrahim1Stephane Isnard2Roger Le Grand3Nathalie Bosquet4Gwenoline Borhis5Yolande Richard6Institut Cochin, Université de Paris, INSERM, CNRS, 75014 Paris, FranceInstitut Cochin, Université de Paris, INSERM, CNRS, 75014 Paris, FranceInstitut Cochin, Université de Paris, INSERM, CNRS, 75014 Paris, FranceUniversité Paris-Saclay, INSERM, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), 92260 Fontenay-aux-Roses, FranceUniversité Paris-Saclay, INSERM, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), 92260 Fontenay-aux-Roses, FranceInstitut Cochin, Université de Paris, INSERM, CNRS, 75014 Paris, FranceInstitut Cochin, Université de Paris, INSERM, CNRS, 75014 Paris, FranceB-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.https://www.mdpi.com/1999-4915/13/2/263B-cellsSIVGCT<sub>FH</sub>CXCL10CXCL13 |
| spellingShingle | Maria Trovato Hany M. Ibrahim Stephane Isnard Roger Le Grand Nathalie Bosquet Gwenoline Borhis Yolande Richard Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen Viruses B-cells SIV GC T<sub>FH</sub> CXCL10 CXCL13 |
| title | Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen |
| title_full | Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen |
| title_fullStr | Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen |
| title_full_unstemmed | Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen |
| title_short | Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen |
| title_sort | distinct features of germinal center reactions in macaques infected by siv or vaccinated with a t dependent model antigen |
| topic | B-cells SIV GC T<sub>FH</sub> CXCL10 CXCL13 |
| url | https://www.mdpi.com/1999-4915/13/2/263 |
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