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  • Review Article
  • Published:

Viral subversion of B cell responses within secondary lymphoid organs

Nature Reviews Immunology volume 18, pages 255–265 (2018)Cite this article

Subjects

Key Points

  • An efficient antibody response to an infecting virus requires the dynamic localization of B cells in unique niches and interaction with neighbouring cells and the local microenvironment.

  • The long relationship between viruses and hosts has resulted in the evolution of several diverse viral strategies that interfere with B cell responses.

  • Virus-induced type I interferon has emerged as a major player that inhibits antiviral humoral immune responses at multiple levels: first, it induces the lymph node recruitment of inflammatory monocytes that inhibit antiviral B cells; second, it promotes the expansion and differentiation of cytotoxic T lymphocytes that kill antiviral B cells; and third, it indirectly supports the differentiation of antiviral B cells into short-lived plasma cells.

  • Further identification of the cellular and molecular mechanisms used by viruses to evade immune control might lead to new treatments for the termination of chronic viral infections and instruct the design of novel, rational vaccines.

Abstract

Antibodies play a crucial role in virus control. The production of antibodies requires virus-specific B cells to encounter viral antigens in lymph nodes, become activated, interact with different immune cells, proliferate and enter specific differentiation programmes. Each step occurs in distinct lymph node niches, requiring a coordinated migration of B cells between different subcompartments. The development of multiphoton intravital microscopy has enabled researchers to begin to elucidate the precise cellular and molecular events by which lymph nodes coordinate humoral responses. This Review discusses recent studies that clarify how viruses interfere with antibody responses, highlighting how these mechanisms relate to our topological and temporal understanding of B cell activation within secondary lymphoid organs.

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Figure 1: Spatiotemporal dynamics of B cell activation.
Figure 2: Viral interference with early B cell activation.
Figure 3: Inflammatory monocytes hinder antiviral B cell responses.
Figure 4: Viral subversion of B cell responses in germinal centres.
Figure 5: Type I interferon-mediated suppression of antibody responses.

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Acknowledgements

The authors thank M. Silva for secretarial assistance, V. Cerundolo, F. V. Chisari, L. G. Guidotti, R. Pardi and Z. Shulman for critical reading of the manuscript and all the members of the Iannacone laboratory for helpful discussions. Work in the Iannacone laboratory discussed in this Review was supported by European Research Council grants 281648 and 725038 (to M.I.), Italian Association for Cancer Research (AIRC) grants 15350 and 9965 (to M.I.), Italian Ministry of Health grant GR-2011-02347925 (to M.I.), Italian Ministry of Education grant SIR-RBSI14BAO5 (to M.K.), Fondazione Regionale per la Ricerca Biomedica grant 2015–0010 (to M.I.), the European Molecular Biology Organization (EMBO) Young Investigator Program (M.I.) and a Career Development Award from the Giovanni Armenise-Harvard Foundation (to M.I.).

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  1. Division of Immunology, Transplantation and Infectious Diseases and Experimental Imaging Center, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Via Olgettina 58, Milan, 20132, Italy

    Mirela Kuka & Matteo Iannacone

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M.I. and M.K. both contributed to the research of data, and the discussion, writing, review and editing of this manuscript.

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Correspondence to Matteo Iannacone.

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Glossary

Multiphoton intravital microscopy

A fluorescence imaging technique that enables the study of cellular interactions in real time within living organisms. It uses infrared lasers that facilitate deep-tissue imaging while limiting phototoxicity and photobleaching.

Clodronate-encapsulated liposomes

Liposomes that contain the drug dichloromethylene diphosphonate. These liposomes are ingested by macrophages, resulting in cell death.

Latency

The ability of certain viruses to establish a reversible dormant state in infected cells with minimal production of viral proteins and absence of progeny virus production.

Polyclonal hypergammaglobulinaemia

Increased levels of nonspecific immunoglobulins in serum that typically occur during chronic viral infections and autoimmune diseases.

Pinocytosis

Also known as fluid-phase endocytosis. A process of engulfment of extracellular fluid and its solutes. It can be mediated by an actin-dependent mechanism that can engulf large volumes (macropinocytosis) or by other mechanisms that result in engulfment of smaller volumes (micropinocytosis).

Lymphopenia

The condition of having an abnormally low level of lymphocytes in the blood.

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Kuka, M., Iannacone, M. Viral subversion of B cell responses within secondary lymphoid organs. Nat Rev Immunol 18, 255–265 (2018). https://doi.org/10.1038/nri.2017.133

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