A landscape for the dynamics of an immune response

Dynamic shaping of the antibody repertoire is essential for effective immunity. We describe here a novel approach for clarifying how the antibody repertoire is shaped over time for development of a specific immune response. We obtained over 500 immunoglobulin G1 clones harboring VH186.2 from the spleen, bone marrow, and microdissected individual germinal centers of (4-hydroxy-3-nitrophenyl) acetyl-immunized C57BL/6 mice at various time points postimmunization. Statistical analyses provided an index for defining clonal diversity and cluster analyses gave us a three-dimensional landscape with which clone distance was visualized with the expression level of antibodies. This landscape approach facilitated our understanding of the dynamics shaping the actual antibody repertoire, in which pre-existing naturally occurring population persisted and provided a significant impact upon the repertoire. To the established model for describing production of the antibody-forming cells, we were able to append an indispensable issue in considering the maturation of humoral immune response.