![]() ![]() A B cell clone includes all B cells originating from one parent B cell that share the same heavy and light chain variable region nucleotide sequences. The B cell immune repertoire can be analyzed quantitatively and qualitatively by sequencing the re-arranged variable region of the heavy chain (HC) of the B cell receptor (BCR) that is unique for each individual B cell or clonally expanded B cell ( Figure 1). Finally, possible short- and long- term implications for vaccine research are highlighted. Current and potential future applications of single cell technology in immune repertoire analysis are then discussed. This review summarizes recent evidence of converging sequences in infectious diseases. This has enabled the cloning of receptors and the functional validation of a predicted specificity. However, only single cell technologies have made it possible to capture the sequence of both heavy and light chains of a BCR or the alpha and beta chains the TCR. Bulk sequencing has shown putatively specific converging sequences after infection or vaccination. In addition, vaccine testing could be simplified if we could predict responses through sequencing BCR and TCRs. Assuming that it is possible to predict which B and T cell receptors will respond to a given immunogen, vaccine strategies could be optimized and personalized. Repertoire diversity may in these cases be a limiting factor for vaccine efficacy. However, there are indications that there are “holes” in the breadth of repertoire diversity, where no or few B or T cell are able to bind to a given antigen. Traditional vaccine development builds on the assumption that healthy individuals have virtually unlimited antigen recognition repertoires of receptors in B cells and T cells. Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore.This allows lymphocyte migration to be controlled at several different steps, leading to a combinatorial increase in specificity and sensitivity. Specific lymphocyte and endothelial adhesion molecules (AM) are involved in each step of this "adhesion cascade" (reviewed in CARLOS and HARLAN 1994 IMHOF and DUNON 1995 BUTCHER and PICKER 1996). Adhesion interactions of vascular endothelium with lymphocytes under flow or shear consist of at least four steps: (I) an initial transient sticking or rolling (2) if the lymphocytes encounter appropriate activating or chemotactic factors in the local environment, rolling may be followed by a lymphocyte activation step that then leads to (3) strong adhesion or sticking that may be followed by (4) lym phocyte diapedesis into tissue (BUTCHER 1991 SHIMUZU et al. ![]() An important feature of this migration is the ability of lymphocytes to recognize and adhere to the surface of blood vessel endothelial cells before migrating through the vessel wall into surrounding tissue (CARLOS and HARLAN 1994 IMHOF and DUNON 1995 BUTCHER and PICKER 1996). Smaller numbers of lymphocytes migrate from blood to extranodal tissues such as pancreas and then through lymphatic vessels to LN (MACKAY et al. Most lymphocytes recirculate throughout the body, migrating from blood through organized lymphoid tissues such as lymph nodes (LN) and Peyer's patches (PP), then to lymph and back to blood (GOWANS and KNIGHT 1964). ![]()
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