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  • Review Article
  • Published:

B-cell responses to vaccination at the extremes of age

Nature Reviews Immunology volume 9, pages 185–194 (2009)Cite this article

Key Points

  • The generation of protective B-cell responses is limited both in early life and in elderly individuals. Infants are vulnerable to infections soon after the disappearance of IgG antibodies of maternal origin, and elderly individuals have problems in dealing with new pathogens and in responding to pathogens that they have previously overcome.

  • Numerous factors concur to limit plasma-cell differentiation in early life, including decreased strength of signals from the B-cell receptor (BCR) and co-stimulatory molecules, decreased antigen availability through binding of maternal antibodies, delayed follicular dendritic cell (FDC) maturation limiting germinal centre reactions and B-cell competition for simultaneous access to limited germinal centre resources. The duration of IgG responses elicited in early life is also shorter than in mature individuals, probably as a result of exposure to a large load of environmental antigens and the restriction of numerous plasmablasts towards a limited set of plasma-cell survival niches in the bone marrow.

  • By contrast, this combination of factors results in the preferential differentiation of early-life B cells towards memory B cells. This does not imply that the magnitude and persistence of these memory responses are mature, as infant-triggered memory B cells might not be life-long.

  • Elderly individuals also have an inability to raise brisk and sustained responses to new antigens. But at the same time they have increasing titres of organ-specific and organ-non-specific autoantibodies, possibly resulting from their generation as by-products of earlier responses to other antigens. The elderly also have an over-representation of specific classes of antibody from individual B-cell clones.

  • Factors that contribute to the inability to raise sustained antibody responses include an age-related decrease in the production of new B cells from their precursors, a progressive shift from mostly naive B cells to mostly memory cells in later years, limitations of B-cell proliferation and/or retention of immune complexes by FDCs resulting in fewer and smaller germinal centre responses, and suboptimal CD40–CD40L interactions between B and T cells.

  • At both extremes of age, potential strategies towards improved vaccine efficacy include the development of delivery systems and immunomodulators that increase the recruitment and production of naive B cells (for example, higher antigen doses, increased antigen retention, improved B-cell targeting and increased stem cell differentiation) and that induce B-cell activation and/or their differentiation into plasma cells, as well as providing boosters as often as necessary to recall antigen-specific memory B cells.

Abstract

Infants and the elderly share a high vulnerability to infections and therefore have specific immunization requirements. Inducing potent and sustained B-cell responses is as challenging in infants as it is in older subjects. Several mechanisms to explain the decreased B-cell responses at the extremes of age apply to both infants and the elderly. These include intrinsic B-cell limitations as well as numerous microenvironmental factors in lymphoid organs and the bone marrow. This Review describes the mechanisms that shape B-cell responses at the extremes of age and how they could be taken into account to design more effective immunization strategies for these high-risk age groups.

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Figure 1: Early-life limitations of B-cell responses.
Figure 2: Comparative changes in the B-cell pool.

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Acknowledgements

The authors are grateful to all who participated in or supported their research projects.

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Authors and Affiliations

  1. Departments of Pathology–Immunology and Pediatrics, WHO Collaborative Center for Neonatal Vaccinology, Medical Faculty of the University of Geneva, Centre Medical Universitaire, 1 rue Michel Servet, Geneva 4, 1211, Switzerland

    Claire-Anne Siegrist

  2. Translational Medicine, Cranfield Health, Vincent Building, Cranfield University, Bedfordshire, MK43 0AL, UK

    Richard Aspinall

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  1. Claire-Anne Siegrist
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  2. Richard Aspinall
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Correspondence to Claire-Anne Siegrist.

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Glossary

Infant

A ≤ 12-month-old human baby or a ≤ 3-week-old mouse (experimental definition).

Neonate

A ≤ 28-day-old human infant or a ≤7-day-old mouse.

T-cell-independent B-cell response

A B-cell response that is elicited without the requirement for CD4+ T-cell co-stimulation, which is a characteristic of responses to most polysaccharide antigens.

T-cell-dependent B-cell response

A B-cell response that requires co-stimulatory signals provided by CD4+ T cells, a characteristic of responses to all protein or conjugate vaccines.

Seroconversion

The development of detectable specific antibodies in the serum as a result of infection or immunization.

Rheumatoid factor

An autoantibody specific for the Fc portion of IgG, which is most relevant in rheumatoid arthritis.

Benign monoclonal gammopathy

A condition in which a low or non-quantifiable level of a monoclonal paraprotein is detected in the blood by protein electrophoresis.

Telomere

A region of repetitive DNA at the end of chromosomes, which protects the end of the chromosome from destruction.

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Siegrist, CA., Aspinall, R. B-cell responses to vaccination at the extremes of age. Nat Rev Immunol 9, 185–194 (2009). https://doi.org/10.1038/nri2508

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