BLyS-mediated modulation of naive B cell subsets impacts HIV Env-induced antibody responses.

TitleBLyS-mediated modulation of naive B cell subsets impacts HIV Env-induced antibody responses.
Publication TypeJournal Article
Year of Publication2012
AuthorsDosenovic P, Soldemo M, Scholz JL, O'Dell S, Grasset EK, Pelletier N, Karlsson MCI, Mascola JR, Wyatt RT, Cancro MP, Karlsson Hedestam GB
JournalJ Immunol
Volume188
Issue12
Pagination6018-26
Date Published2012 Jun 15
ISSN1550-6606
KeywordsAIDS Vaccines, Animals, Antibodies, Neutralizing, B-Cell Activating Factor, B-Lymphocyte Subsets, env Gene Products, Human Immunodeficiency Virus, Enzyme-Linked Immunosorbent Assay, Epitopes, B-Lymphocyte, Flow Cytometry, HIV Antibodies, Humans, Immunohistochemistry, Mice, Mice, Inbred BALB C, Microscopy, Confocal, Recombinant Proteins, Transfection
Abstract

Neutralizing Abs provide the protective effect of the majority of existing human vaccines. For a prophylactic vaccine against HIV-1, broadly neutralizing Abs targeting conserved epitopes of the viral envelope glycoproteins (Env) are likely required, because the pool of circulating HIV-1 variants is extremely diverse. The failure to efficiently induce broadly neutralizing Abs by vaccination may be due to the use of suboptimal immunogens or immunization regimens, or it may indicate that B cells specific for broadly neutralizing Env determinants are selected against during peripheral checkpoints, either before or after Ag encounter. To investigate whether perturbation of B cell subsets prior to immunization with recombinant Env protein affects the vaccine-induced Ab response in mice, we used B lymphocyte stimulator (BLyS), a cytokine that regulates survival and selection of peripheral B cells. We show that the transient BLyS treatment used in this study substantially affected naive B cell populations; in particular, it resulted in more B cells surviving counter-selection at the transitional stages. We also observed more mature naive B cells, especially marginal zone B cells, in BLyS-treated mice. Intriguingly, provision of excess BLyS prior to immunization led to a consistent improvement in the frequency and potency of HIV-1 Env vaccine-induced neutralizing Ab responses, without increasing the number of Env-specific Ab-secreting cells or the Ab-binding titers measured after boosting. The results presented in this article suggest that an increased understanding of BLyS-regulated processes may help the design of vaccine regimens aimed at eliciting improved neutralizing Ab responses against HIV-1.

DOI10.4049/jimmunol.1200466
Alternate JournalJ. Immunol.
PubMed ID22561155