title: Tissue-specific B-cell dysfunction and generalized memory B-cell loss during acute SIV infection.
abstract: BACKGROUND
  Primary HIV-infected patients display severe and irreversible damage to different blood B-cell subsets which is not restored by highly efficient anti-retroviral therapy (HAART). Because longitudinal investigations of primary HIV-infection is limited by the availability of lymphoid organs, we studied the tissue-specific B-cell dysfunctions in acutely simian immunodeficiency virus (SIV) mac251-infected Cynomolgus macaques.
  
  
  RESULTS
  Experiments were performed on three groups of macaques infected for 14, 21 or 28 days and on three groups of animals treated with HAART for two-weeks either initiated at 4 h, 7 or 14 days post-infection (p.i.). We have simultaneously compared changes in B-cell phenotypes and functions and tissue organization of B-cell areas in various lymphoid organs. We showed that SIV induced a steady decline in SIgG-expressing memory (SIgD(-)CD27(+)) B-cells in spleen and lymph nodes during the first 4 weeks of infection, concomitant to selective homing/sequestration of B-cells to the small intestine and spleen. SIV non-specific Ig production was transiently increased before D14p.i., whereas SIV-specific Ig production was only detectable after D14p.i., coinciding with the presence of CD8(+) T-cells and IgG-expressing plasma cells within germinal centres. Transient B-cell apoptosis on D14p.i. and commitment to terminal differentiation contributed to memory B-cell loss. HAART abrogated B-cell apoptosis, homing to the small intestine and SIV-specific Ig production but had minimal effect on early Ig production, increased B-cell proportions in spleen and loss of memory B-cells. Therefore, virus-B-cell interactions and SIV-induced inflammatory cytokines may differently contribute to early B-cell dysfunction and impaired SIV/HIV-specific antibody response.
  
  
  CONCLUSIONS
  These data establish tissue-specific impairments in B-cell trafficking and functions and a generalized and steady memory B-cell loss in secondary lymphoid organs. Characterization of underlying mechanisms would be helpful in designing new therapeutic strategies to dampen B-cell activation and increases HIV/SIV specific antibody response.
authors: Atomic Energy Commission, Institute of Emerging Diseases and Innovative Therapies, Division of Immuno-Virology, UMR-E1, Univ. Paris-Sud, Orsay, France.
authors: Sandrine
authors: S
authors: Peruchon
authors: Nada
authors: N
authors: Chaoul
authors: Chantal
authors: C
authors: Burelout
authors: Benoit
authors: B
authors: Delache
authors: Patricia
authors: P
authors: Brochard
authors: Pascale
authors: P
authors: Laurent
authors: Fabrice
authors: F
authors: Cognasse
authors: Sophie
authors: S
authors: Prévot
authors: Olivier
authors: O
authors: Garraud
authors: Roger
authors: R
authors: Le Grand
authors: Yolande
authors: Y
authors: Richard
mesh_terms: D000818:Animals; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry; D007156:Immunologic Memory; D007249:Inflammation; D007700:Kinetics; D008198:Lymph Nodes / Q000473:pathology; D008252:Macaca fascicularis; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D013997:Time Factors
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G