CHEMOKINE-GUIDED IMMUNE CELL MIGRATION IN LYMPH NODES

The principal function of secondary lymphoid organs, such as the lymph nodes, is to bring antigen-presenting cells and antigen-specific B and T cells into close physical contact with each other. This complex cellular rendezvous is critical for mounting an effective immune response. Cells often travel great distances to reach these specialized organs and make precise moves to different regions within them, guided only by a complicated set of highly redundant factors called chemokines.

1. Chemokines, along with adhesion molecules, significantly contribute to the massive extravasation of lymphocytes into lymph nodes via high endothelial venules.
2. Once lymphocytes have exited the vascular compartment, they differentially migrate to B and T cell zones in the cortex and paracortex, respectively, under the influence of chemokines secreted from lymph node stromal cells and follicular and interdigitating dendritic cells (DCs).
3. Guided by chemokines, immature DCs in the periphery encounter antigen, begin their maturation program, and migrate via the lymphatics to the node. DCs that matured en route present antigen to T cells in the paracortex, which differentiate, modify their chemokine receptor profile and exit the node via efferent lymphatics.
4. Antigen may also enter the lymph node either complexed with antibody or alone. Raw antigen may be taken up by interdigitating DCs and presented to naïve T cells. It may also be taken up and presented by naïve B cells. The now activated T cells interact with antigen-presenting B cells and elicit the generation of memory and plasma B cells.
5. Antibody-antigen complexes bind Fc receptors on the surface of follicular DCs. Antigen on the surface of DCs stimulates nearby naïve B cells. Activated B and T cells migrate toward the marginal zone and interact to encourage B cell differentiation into memory and plasma B cells.

Chemokine Poster References

• Christopherson II, K. & R. fHromas (2001) Stem Cells 19:388.
• Murphy, P.M. (2000) Pharmacol. Rev. 52:145.
• Murphy, P.M. (2002) Pharmacol. Rev. 54:227.
• Rossi, D. & A. Zlotnik (2000) Annu. Rev. Immunol. 18:217.
• Rot, A. & U.H. von Adrian (2004) Annu Rev. Immunol. 22:891.

• Cupedo, T. & R.E. Mebius (2003) Sem. Immunol.15:243.
• Müller, G. et al. (2003) Immunol. Rev. 195:117.
• Ohl, L. et al. (2003) Sem. Immunol. 15:249.
• Schmid-Schönbein, G.W. (2003) Lymphatic Res. Biol.1:25.

• Campbell, D.J. et al. (2003) Immunol. Rev. 195:58.
• Wei, S.H. et al. (2003) Immunol. Rev. 195:136.
• Müller, G. et al. (2002) J. Leukoc. Biol. 72:1.

• Cyster, J.G. (2003) Immunol. Rev. 194:48.
• Kunkel, E.J. & E.C. Butcher (2003) Nat. Rev. Immunol. 3:822.
• Vinuesa, C.G. & M.C. Cook (2001) Curr. Mol. Med. 1:689.

• Gunn, M.D. (2003) Sem. Immunol. 15:271.

• Campbell, D.J. et al. (2003) Sem. Immunol.15:277.
• Schaerli, P. & B. Moser (2005) Immunol. Res. 31:57.
• Weninger, W. & U.H. von Adrian (2003) 15:257.