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  • Review Article
  • Published:

B cells in HIV infection and disease

Nature Reviews Immunology volume 9, pages 235–245 (2009)Cite this article

Key Points

  • HIV infection leads to perturbations of all of the main cell types of the immune system, including B cells. Most B-cell perturbations are associated with indirect effects of ongoing HIV replication, although some perturbations arise regardless of the decrease in viraemia by effective antiretroviral therapy (ART).

  • Many B-cell defects in HIV infection are associated with alterations in the B-cell subpopulations that circulate in the peripheral blood. Most B cells in healthy individuals comprise resting naive and memory B cells, whereas several minor subpopulations are over-represented in HIV-infected individuals, including immature transitional B cells, exhausted B cells, activated mature B cells and plasmablasts.

  • In vitro and in vivo studies show that HIV can also interact directly with B cells, although the frequency of these interactions is unlikely to account for the extent of B-cell dysregulation that is observed in infected individuals. HIV virions complexed with complement and antibody can bind B cells through the complement receptor CD21, and HIV virions and proteins, including gp120 and Nef, can also interact directly or indirectly with B cells.

  • Indirect effects of HIV viraemia on B cells include B-cell hyperactivity (as manifested by hypergammaglobulinaemia), increased B-cell polyclonal activation, increased B-cell turnover, increased expression of activation markers and of markers that are associated with activation-induced apoptosis, increased frequency of B-cell malignancies and increased differentiation of B cells to plasmablasts.

  • HIV viraemia with CD4+ T-cell lymphopenia is associated with an increased frequency of immature transitional B cells. This increase is also associated with increased serum levels of interleukin-7.

  • HIV viraemia leads to B-cell exhaustion, as manifested by increased expression of multiple inhibitory receptors, altered expression of homing receptors, decreased cell division and somatic hypermutation in vivo, decreased proliferative and effector properties in vitro and enrichment of HIV-specific responses in the exhausted B-cell compartment.

  • Although most B-cell perturbations in HIV-infected individuals are attributed to viraemia and are reversible by ART, one important exception is the loss of memory B cells. All stages of HIV infection are associated with a decrease both in the frequency of resting memory B cells and of B-cell responses against T-cell-dependent and T-cell-independent antigens.

  • Many B-cell perturbations observed in HIV infection also arise in various infectious and non-infectious disease settings that involve immune dysfunction. Several human diseases that affect B cells show dysregulation of immature transitional B cells, whereas others show dysregulation of memory B cells, with alterations that are similar to B-cell exhaustion and activation-induced terminal differentiation.

Abstract

In recent years, intense research efforts have been dedicated to elucidating the pathogenic mechanisms of HIV-associated disease progression. In addition to the progressive depletion and dysfunction of CD4+ T cells, HIV infection also leads to extensive defects in the humoral arm of the immune system. The lack of immune control of the virus in almost all infected individuals is a great impediment to the treatment of HIV-associated disease and to the development of a successful HIV vaccine. This Review focuses on advances in our understanding of the mechanisms of B-cell dysfunction in HIV-associated disease and discusses similarities with other diseases that are associated with B-cell dysfunction.

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Figure 1: HIV-induced alterations of human B-cell subpopulations.
Figure 2: Direct and indirect effects of HIV replication on B cells.
Figure 3: B-cell exhaustion induced by persistent HIV infection and ongoing viral replication.

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Acknowledgements

We thank T. W. Chun, J. Chen and A. Waldner for suggestions on the manuscript and help with the figures. This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA.

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  1. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, 20892, Maryland, USA

    Susan Moir & Anthony S. Fauci

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  1. Susan Moir
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Correspondence to Susan Moir.

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Glossary

Combination antiretroviral therapy

Multi-drug therapy used to suppress viral replication and minimize viral resistance.

Memory B cell

A quiescent antigen-experienced B cell that can rapidly differentiate into a plasma cell on re-exposure to antigen.

Switched or unswitched antibody isotypes

Class switching of the immunoglobulin heavy chain from IgM and IgD to IgG or IgA or IgE allows the diversification of the antibody repertoire, generating antibody isotypes with the same antigen specificity but with different effector functions.

Plasmablast

An antibody-secreting precursor of the non-dividing plasma cell that has the capacity to divide and migrate.

Hypergammaglobulinaemia

Increased levels of immunoglobulin in blood serum.

Idiopathic CD4+ T-cell lymphocytopenia

A disorder of unknown cause that is characterized by decreased CD4+ T-cell counts in the absence of evidence for HIV-1 or HIV-2 infection or any known immunodeficiency or therapy associated with decreased levels of CD4+ T cells.

IgM+ memory B cell

An unswitched CD27+ memory B cell circulating in the peripheral blood that might be related to marginal zone B cells.

Marginal zone B cell

A mature B cell that is enriched anatomically in the marginal zone of the spleen, which is the interface between red pulp and white pulp.

Systemic lupus erythematosus

An autoimmune disease that is characterized by the potential for multiorgan involvement and production of antibodies that are specific for components of the cell nucleus.

Common variable immunodeficiency

A primary immunodeficiency disease with a heterogeneous cause and phenotype that is characterized by hypogammaglobulinaemia.

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Moir, S., Fauci, A. B cells in HIV infection and disease. Nat Rev Immunol 9, 235–245 (2009). https://doi.org/10.1038/nri2524

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