ABSTRACT
Introduction 267 Lymphocyte recirculation and homing 267 Lymphocytes: licensed to move 267 Lymphocyte-endothelial interaction, a multistep process 270 Tissue-specific lymphocyte homing 270 The molecular basis of lymphoma dissemination 273
The dissemination of T-lineage lymphomas 273 The dissemination of B-lineage lymphomas 274 Homing of normal plasma cells and myeloma cells 275 Conclusion 275 Key points 276 References 276
Specific recognition of foreign antigens and effective surveillance are the two mainstays of the body’s defense against microbial invasion. Evolution has created great antigen-receptor diversity and has equipped lymphocytes with exquisite motility and migratory properties to accomplish these tasks. As discovered more than four decades ago by Gowans and Knight, mature lymphocytes recirculate, moving continuously from blood to tissue and back to the bloodstream again.1 This recirculation is not random, but is guided by mechanisms allowing lymphocyte diapedesis at the correct site and directing their migration to the proper place in the tissues (for reviews, see 2-5]. Within the tissues, lymphocytes display a characteristic ‘amoeboid’ form of cell migration,6 which represents a physically optimized migration mode that allows easy cell traffic toward and between different tissue compartments. This movement is directed by chemokines and stromal cell networks in the lymphoid microenvironments.7,8 Lymphocyteendothelial recognition plays a central role in controlling the access of specialized lymphocyte subsets to particular tissues, thus influencing the nature of local immune and inflammatory responses. At the molecular level, this ‘homing’ process is regulated by adhesion molecules in concert with chemokines (chemoattractant cytokines): lymphocyte subsets as well as endothelial cells specifically program their expression of adhesion molecules and chemokines/chemokine receptors, allowing lymphocytes
the immune system, such as the mucosal-associated lymphoid tissue (MALT) and the skin.2-5
This chapter describes the basic principles of lymphocyte trafficking and discusses emerging evidence indicating that the molecular cues regulating this process also play a critical role in lymphoma dissemination. In cases of malignant transformation, the fact that lymphocytes are ‘licensed to move’ forms a serious threat to the organism, since it allows rapid tumor dissemination irrespective of the conventional anatomic boundaries limiting tumor spread in most solid tumors. The strikingly tissue-specific dissemination of, for example, malignant lymphomas of the mucosalassociated lymphoid tissues, cutaneous lymphomas, and multiple myeloma reflect basic rules of lymphocyte homing. A better understanding of the molecular mechanisms underlying this behavior may provide novel targets for treatment of lymphoma patients. For the convenience of the reader, an overview of the most important adhesion molecules and chemokine receptors involved in homing, their distribution on various lymphocyte subsets and non-Hodgkin lymphoma (NHL) subtypes, and their ligands, sites of interaction, and predominant role(s) in homing are given in Table 16.1.
