Imaging the immune system

In 1997, Immunological Reviews published a volume entitled ‘The anatomy of antigen-specific immune responses’ (1). This was a timely topic because of a new wave of research that shed light on how antigen-specific lymphocytes become activated within the lymphoid organs. The major experimental approach was an old one – immunohistology. As in the past, enzyme-labeled antibodies specific for T cells, B cells, dendritic cells, or macrophages were used to color the various compartments of the involved lymphoid organs. The new twist was that antigenspecific lymphocytes could be identified at the same time. In the case of B cells, this was accomplished by using labeled haptenated antigens to stain B cells expressing complementary immunoglobulins. Hapten-specific B-cell responses were particularly amenable to this approach, because the frequency of such B cells within the polyclonal repertoire was unusually high, thus facilitating their detection. Using this type of system, pioneers like Kelsoe (2) and MacLennan (3) and others documented the early proliferation of hapten-specific B cells in the follicles and subsequent commitment of some cells to the germinal center reaction and others to the extrafollicular plasma cell pathway. Parallel work used anti-T-cell receptor (TCR) Vb antibodies to measure the expansion of superantigen-specific T cells in both the paracortical regions of lymph nodes and the periarteriolar sheath of spleen (4). Antigen-receptor transgenic animals containing large numbers of lymphocytes of known antigen specificity allowed the development of adoptive transfer experiments in which the anatomy of the primary immune response could be studied (1). For example, injection of peptide-pulsed, fluorescent dye-labeled dendritic cells into mice containing a transferred TCR transgenic T-cell population specific for the peptide showed that antigen presentation to naive T cells occurs in the paracortex of the lymph node (5,6). A similar approach was used to study the anatomy of T-cell help to B cells. Mice containing transferred TCR transgenic CD4 T cell and B-cell receptor (BCR) Marc K. Jenkins