Volume 9 Supplement 2

AIDS Vaccine 2012

Open Access

Lack of IgA envelope-reactive antibody producing cells in terminal ileum in early and chronic HIV-1 infection

  • AM Trama1,
  • H Liao1,
  • A Foulger1,
  • DJ Marshall1,
  • JF Whitesides1,
  • R Parks1,
  • R Meyerhoff1,
  • KE Lloyd1,
  • M Donathan1,
  • J Lucas1,
  • K Soderberg1,
  • TB Kepler2,
  • N Vandergrift1,
  • N Yates1,
  • GD Tomaras1,
  • MA Moody1 and
  • BF Haynes1
Retrovirology20129(Suppl 2):P201

https://doi.org/10.1186/1742-4690-9-S2-P201

Published: 13 September 2012

Background

HIV-1 vaccines must induce protective antibodies at mucosal surfaces; the role of IgA in protection remains unknown. The HIV-1 Env antibody response begins ~day 17 after transmission, and derives from a polyreactive memory B cell pool of gut flora-reactive IgG1 and IgA B cells. Whereas the IgG Env antibody response persists years after acute HIV-1 infection, the initial IgA response decreases over the first month. There is also selective destruction of terminal ileum germinal centers in early HIV-1 infection (EHI). To determine HIV-1 IgA responses in gut, we isolated Env-reactive antibodies from ileum from patients in EHI and chronic HIV-1 infection (CHI).

Methods

Single plasma cells (PCs) and IgD- memory B cells were sorted from the ileum and/or blood of 7 EHI and 3 CHI. Antibodies were isolated by PCR amplification of Ig heavy chain V(D)J and light chain VJ genes and characterized by ELISA and Luminex.

Results

Whereas CHI blood memory IgA+ B cells reactive with HIV-1 envelope ranged from 0.20-0.79%, only 0-0.07% of ileum IgA+ B cells were Env-reactive. Of 254 mAbs isolated from EHI ileum, only 3 (1.2%) were HIV-1-reactive. In CHI, 9 (5.7%) of 158 mAb were HIV-1 reactive. None of the HIV-1 reactive ileum antibodies were of the IgA isotype.

Conclusion

HIV-1 envelope reactive IgA+ memory B cells and PCs can be found in the blood, but there is a dearth of HIV-1 reactive memory IgA+ B cells and PCs in ileum in EHI and CHI. Loss of IgA in plasma after acute HIV-1 infection is paralleled by the loss of IgA+ B cells in ileum, and is likely a consequence of HIV-1-induced ileum germinal center apoptosis. For vaccine design, it will be important to determine if mucosal IgA+ B cell loss is due to replicating virus or is triggered by soluble HIV-1 envelope.

Authors’ Affiliations

(1)
Duke University
(2)
Boston University

Copyright

© Trama et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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