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  • Review Article
  • Published:

Marginal-zone B cells

Nature Reviews Immunology volume 2, pages 323–335 (2002)Cite this article

Key Points

  • Naive, long-lived B cells in rodents and humans are heterogeneous in phenotype, topography and functions. Follicular recirculating B cells populate follicles in the spleen and lymph nodes; static marginal-zone (MZ) B cells are enriched in the MZ of the spleen; and B1 cells recirculate between the blood and the body cavities.

  • Different B-cell clones are enriched with various B-cell subsets by means of a mechanism of positive selection, maturation and maintenance.

  • Selection of the MZ repertoire depends on the rate of clonal production and the specific molecular signals that are received, in part through the B-cell clonal receptor (BCR).

  • Clonal signals through BCRs integrate with signals for survival (through the tumour-necrosis-factor receptor family) and movement (through G-protein-coupled receptors) in regulating the selection and function of MZ B cells.

  • In vitro, MZ B cells present antigen to T cells faster and more efficiently than follicular B cells.

  • Favoured by their location and easy triggering, MZ and B1 B cells are early participants in in vivo T-cell-independent antigen responses and generate a vigorous plasma-cell response.

  • MZ alterations are associated with various autoimmune conditions in both mouse and human.

Abstract

Recent advances in genomics and proteomics, combined with the facilitated generation and analysis of transgenic and gene-knockout animals, have revealed new complexities in classical biological systems, including the B-cell compartment. Studies on an 'old', but poorly characterized, B-cell subset — the naive, marginal-zone (MZ) B-cell subset — over the past two years have spawned an avalanche of data that encompass the generation and function of these cells. Now that the initial 'infatuation' is over, it is time to reconsider these data and generate some conclusions that can be incorporated into a working model of the B-cell system.

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Figure 1: Selection into effector (plasma-cell) and effector-precursor (B1 and MZ) compartments favours a diverse and complete repertoire.
Figure 2: Model summarizing the signals that are involved in MZ B-cell generation, maintenance and function.
Figure 3: MZ B cells and 'natural immunity' function early in blood-borne antigen removal.

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Acknowledgements

We would like to thank P. Balogh (University of Pecs, Hungary) for the anti-endothelial antibody IBL7/1.

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  1. Division of Developmental and Clinical Immunology, Department of Microbiology, University of Alabama at Birmingham, Birmingham, 35294-3300, Alabama, USA

    Flavius Martin & John F. Kearney

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  1. Flavius Martin
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Correspondence to John F. Kearney.

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BTK

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Glossary

NEONATAL TOLERANCE

Functional status of the newborn immune system — discovered by Billingham, Brent and Medawar — that is characterized by the inability to reject allografts.

ALLELIC EXCLUSION

Property of lymphocytes to express a clonal receptor that is derived from only one of the two genetic loci.

Rag-KNOCKOUT MICE

Mice in which a recombination-activating gene (Rag1 or Rag2) has been knocked out; as a result, these mice are not able to generate mature T and B cells.

SCID MICE

Severe combined immunodeficient mice with a spontaneous mutation in the DNA protein kinase that results in a lack of mature T and B cells.

BURSA OF FABRICIUS

Lymphoid organ giving rise to B cells that is located at the junction of the cloaca and gut in birds.

NOTCH

A Drosophila gene that is required in ectodermal cells to prevent differentiation into neuroblasts. Mammalian homologues have been described to have roles in cell-fate specification in various systems.

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Martin, F., Kearney, J. Marginal-zone B cells. Nat Rev Immunol 2, 323–335 (2002). https://doi.org/10.1038/nri799

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