Søren Egedal Degn

The clonal selection theory first proposed by Macfarlane Burnet is a cornerstone of immunology ( 1 ). At the time, it revolutionized the thinking of immunologists because it provided a simple explanation for lymphocyte specificity, immunological memory, and elimination of self-reactive clones ( 2 ). The experimental demonstration by Nossal & Lederberg ( 3 ) that B lymphocytes bear receptors for a single antigen raised the central question of where B lymphocytes encounter antigen. This question has remained mostly unanswered until recently. Advances in techniques such as multiphoton intravital microscopy ( 4, 5 ) have provided new insights into the trafficking of B cells and their antigen. In this review, we summarize these advances in the context of our current view of B cell circulation and activation.