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Widespread B cell perturbations in HIV-1 infection afflict naive and marginal zone B cells.


ABSTRACT: Perturbations in B cells are a hallmark of HIV-1 infection. This is signified by increased numbers of exhausted CD21neg memory B cells, driven by continuous antigen-specific and bystander activation. Using high-dimensional flow cytometry, we demonstrate that this exhausted phenotype is also prevalent among peripheral antigen-inexperienced naive and marginal zone (MZ) B cells in acute and chronic HIV-1 infection. A substantial fraction of naive and MZ B cells exhibit down-regulated CD21 levels and diminished response to B cell receptor (BCR)-dependent stimulation. Compared with CD21pos subsets, the CD21neg naive and MZ B cells differ in the expression of chemokine receptors and activation markers. Effective antiretroviral treatment normalizes peripheral naive and MZ B cell populations. Our results emphasize a more widely spread impairment of B cells in HIV-1 infection than previously appreciated, including antigen-inexperienced cells. This highlights the importance of monitoring functional capacities of naive B cells in HIV-1 infection, as exhausted CD21neg naive B cells may severely impair induction of novel B cell responses.

SUBMITTER: Liechti T 

PROVIDER: S-EPMC6719425 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Widespread B cell perturbations in HIV-1 infection afflict naive and marginal zone B cells.

Liechti Thomas T   Kadelka Claus C   Braun Dominique L DL   Kuster Herbert H   Böni Jürg J   Robbiani Melissa M   Günthard Huldrych F HF   Trkola Alexandra A  

The Journal of experimental medicine 20190620 9


Perturbations in B cells are a hallmark of HIV-1 infection. This is signified by increased numbers of exhausted CD21<sup>neg</sup> memory B cells, driven by continuous antigen-specific and bystander activation. Using high-dimensional flow cytometry, we demonstrate that this exhausted phenotype is also prevalent among peripheral antigen-inexperienced naive and marginal zone (MZ) B cells in acute and chronic HIV-1 infection. A substantial fraction of naive and MZ B cells exhibit down-regulated CD2  ...[more]

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