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  • Review Article
  • Published:

Plasma-cell homing

Nature Reviews Immunology volume 3, pages 822–829 (2003)Cite this article

Key Points

  • Chemokines work together with adhesion molecules to coordinate the migration of IgA and IgG antibody-secreting cells (ASCs) to target effector tissues.

  • IgA ASCs that arise in the lymphoid tissues of the upper aerodigestive tract mainly traffic to non-intestinal mucosal sites, whereas IgA ASCs that develop in lymphoid tissues of the intestine can migrate to both intestinal and non-intestinal epithelial tissues. This process is mediated by differential expression of integrins and chemokine receptors.

  • Early ASCs downregulate the expression of chemokine receptors for lymphoid-tissue chemokines and upregulate the expression of chemokine receptors that are used for trafficking to effector sites.

  • Both IgG and IgA ASCs might use CXC-chemokine receptor 4 (CXCR4) for trafficking to the bone marrow.

  • IgG ASCs upregulate the expression of CXCR3, which they probably use for trafficking to sites of inflammation.

  • Upregulation of CC-chemokine receptor 9 (CCR9) expression by ASCs that are primed by small intestinal antigens probably focuses their migration back to the small intestine.

  • The expression of CCR10 is upregulated by IgA ASCs throughout the body and, together with specific integrins, allows IgA ASCs to disseminate to many effector tissues.

  • Further study will be required to assess the roles of chemokines in plasma-cell retention and survival, to elucidate the regulatory mechanisms that underlie the co-expression of IgA with mucosal chemokine receptors and IgG with inflammatory chemokine receptors, and to characterize the trafficking properties of IgE ASCs.

Abstract

Recent studies indicate that chemoattractant cytokines (chemokines), together with tissue-specific adhesion molecules, coordinate the migration of antibody-secreting cells (ASCs) from their sites of antigen-driven differentiation in lymphoid tissues to target effector tissues. Developing ASCs downregulate the expression of receptors for lymphoid tissue chemokines and selectively upregulate the expression of chemokine receptors that might target the migration of IgA ASCs to mucosal surfaces, IgG ASCs to sites of tissue inflammation and both types of ASC to the bone marrow — an important site for serum antibody production. By directing plasma-cell homing, chemokines might help to determine the character and efficiency of mucosal, inflammatory and systemic antibody responses.

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Figure 1: IgA and IgG antibody-secreting cells (ASCs) have distinctive trafficking patterns that depend on their site of induction.
Figure 2: Changes in the expression of chemokine receptors during B-cell differentiation.
Figure 3: Model of trafficking of IgA and IgG ASCs mediated by specific adhesion molecules and chemokine receptors.

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Acknowledgements

We thank N.H. Lazarus for input into this manuscript. This work was supported by the United States Public Health Service and the Department of Veterans Affairs.

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Authors and Affiliations

  1. Bioseek, Inc., Burlingame, 94010, California, USA

    Eric J. Kunkel

  2. Department of Pathology, Laboratory of Immunology and Vascular Biology, Stanford University School of Medicine, Stanford, 94305, California

    Eugene C. Butcher

  3. The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, 94304, California, USA

    Eugene C. Butcher

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  1. Eric J. Kunkel
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Correspondence to Eric J. Kunkel.

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DATABASES

LocusLink

CCL19

CCL20

CCL21

CCL25

CCL27

CCL28

CCR6

CCR7

CCR9

CD38

CXCL9

CXCL10

CXCL12

CXCL13

CXCL16

CXCR3

CXCR4

CXCR5

CXCR6

L-selectin

MADCAM1

VCAM1

FURTHER INFORMATION

Eugene Butcher's lab

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Kunkel, E., Butcher, E. Plasma-cell homing. Nat Rev Immunol 3, 822–829 (2003). https://doi.org/10.1038/nri1203

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