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Default in plasma and intestinal IgA responses during acute infection by simian immunodeficiency virus

Nada Chaoul12, Chantal Burelout12, Sandrine Peruchon123, Beatrice Nguyen van Buu45, Pascale Laurent45, Alexis Proust67, Martine Raphael67, Olivier Garraud3, Roger Le Grand12, Sophie Prevot45 and Yolande Richard1289*

Author Affiliations

1 Commissariat à l’Energie Atomique (CEA), CEA, Institut des Maladies Emergentes et Thérapies Innovantes Service d’Immuno-Virologie, CEA, Fontenay-aux Roses, F-92260, France

2 Université Paris-Sud, Orsay, F-91060, France

3 EA3064 Université de Lyon, Faculté de Médecine et Etablissement Français du Sang (EFS) Auvergne-Loire, Saint Etienne, F-42023, France

4 Service d’Anatomie et Cytologie pathologiques, AP-HP, Hôpital A. Béclère, Clamart, F-92140, France

5 Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, F-94276, France

6 Service d’Hématologie et Immunologie Biologiques, cytogénétique, CHU-Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin-Bicêtre, F-94 724, France

7 INSERM U802, Université Paris-Sud, Le Kremlin-Bicêtre, F-94 724, France

8 Inserm U1016, Institut Cochin, Paris, France

9 CNRS UMR8104, Paris, France. Institut Cochin. Département d’Immunologie. 27, Rue du Faubourg St Jacques, Paris, F-75014, France

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Retrovirology 2012, 9:43  doi:10.1186/1742-4690-9-43

Published: 25 May 2012

Abstract

Background

Conflicting results regarding changes in mucosal IgA production or in the proportions of IgA plasma cells in the small and large intestines during HIV-infection have been previously reported. Except in individuals repeatedly exposed to HIV-1 but yet remaining uninfected, HIV-specific IgAs are frequently absent in mucosal secretions from HIV-infected patients. However, little is known about the organization and functionality of mucosal B-cell follicles in acute HIV/SIV infection during which a T-dependent IgA response should have been initiated. In the present study, we evaluated changes in B-cell and T-cell subsets as well as the extent of apoptosis and class-specific plasma cells in Peyer’s Patches, isolated lymphoid follicles, and lamina propria. Plasma levels of IgA, BAFF and APRIL were also determined.

Results

Plasma IgA level was reduced by 46% by 28 days post infection (dpi), and no IgA plasma cells were found within germinal centers of Peyer’s Patches and isolated lymphoid follicles. This lack of a T-dependent IgA response occurs although germinal centers remained functional with no sign of follicular damage, while a prolonged survival of follicular CD4+ T-cells and normal generation of IgG plasma cells is observed. Whereas the average plasma BAFF level was increased by 4.5-fold and total plasma cells were 1.7 to 1.9-fold more numerous in the lamina propria, the relative proportion of IgA plasma cells in this effector site was reduced by 19% (duodemun) to 35% (ileum) at 28 dpi.

Conclusion

Our data provide evidence that SIV is unable to initiate a T-dependent IgA response during the acute phase of infection and favors the production of IgG (ileum) or IgM (duodenum) plasma cells at the expense of IgA plasma cells. Therefore, an early and generalized default in IgA production takes place during the acute of phase of HIV/SIV infection, which might impair not only the virus-specific antibody response but also IgA responses to other pathogens and vaccines as well. Understanding the mechanisms that impair IgA production during acute HIV/SIV infection is crucial to improve virus-specific response in mucosa and control microbial translocation.

Keywords:
Mucosal B-cell response; IgA; HIV/SIV; Germinal centers; BAFF; Terminal ileum