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Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen
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Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen
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Journal Article
Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen
2021
Overview
B-cell follicles constitute large reservoirs of infectious HIV/SIV associated to follicular dendritic cells and infecting follicular helper (TFH) and regulatory (TFR) 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 TFH massively polarized into TFH1-like cells, by inflammation-induced recruitment of fCD8 (either regulatory or cytotoxic) and by low numbers of TFR limiting TFH/TFR competition for high affinity B-cells. Increased GC B-cells apoptosis and accumulation of CD21lo 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.
Publisher
MDPI AG,MDPI
Subject
/ Animals
/ Antigens
/ B-Cell Activation Factor Receptor - metabolism
/ B-cells
/ CD4-Positive T-Lymphocytes - immunology
/ CD4-Positive T-Lymphocytes - metabolism
/ CXCL10
/ CXCL13
/ Germinal Center - immunology
/ HIV
/ Human immunodeficiency virus
/ lymph
/ Male
/ Plasma
/ Simian Acquired Immunodeficiency Syndrome - immunology
/ Simian Immunodeficiency Virus - immunology
/ SIV
/ Spleen
/ T Follicular Helper Cells - immunology
/ T Follicular Helper Cells - metabolism
/ T-Lymphocyte Subsets - immunology
/ T-Lymphocyte Subsets - metabolism
/ Tetanus
/ Tetanus Toxoid - administration & dosage
/ TFH
/ Transmembrane Activator and CAML Interactor Protein - metabolism
/ Vaccines
