T cell–dependent immune responses develop soon after birth, whereas it takes 2 yr for humans to develop T cell–independent responses. We used this dissociation to analyze the repertoire diversification of IgM+IgD+CD27+ B cells (also known as “IgM memory” B cells), comparing these cells with switched B cells in children <2 yr of age, with the aim of determining whether these two subsets are developmentally related. We show that the repertoire of IgM+IgD+CD27+ B cells in the spleen and blood displays no sign of antigen-driven activation and expansion on H-CDR3 spectratyping, despite the many antigenic challenges provided by childhood vaccinations. This repertoire differed markedly from those of switched B cells and splenic germinal center B cells, even at the early stage of differentiation associated with μ heavy chain expression. These data provide evidence for the developmental diversification of IgM+IgD+CD27+ B cells, at least in very young children, outside of T cell–dependent and –independent immune responses.

The fact that you can vaccinate a child at 5 years of age and find lymphoid B cells and antibodies specific for this vaccination 70 years later remains an immunologic enigma. It has never been determined how these long-lived memory B cells are maintained and whether they are protected by storage in a special niche. We report that, whereas blood and spleen compart-

The unwarranted persistence of the immunoinflammatory process turns this critical component of the body’s natural defenses into a destructive mechanism, which is involved in a wide range of diseases, including chronic rejection. Performing a comprehensive analysis of human kidney grafts explanted because of terminal chronic rejection, we observed that the inflammatory infiltrate becomes organized into an ectopic lymphoid tissue, which harbors the maturation of a local humoral immune response. Interestingly, intragraft humoral immune response appeared uncoupled from the systemic response because the repertoires of locally produced and circulating alloantibodies only minimally overlapped. The organization of the immune effectors within adult human inflamed tissues recapitulates the biological program recently identified in murine embryos during the ontogeny of secondary lymphoid organs. When this recapitulation was incomplete, intragraft B cell maturation was impeded, limiting the aggressiveness of the local humoral response. Identification of the molecular checkpoints critical for completion of the lymphoid neogenesis program should help develop innovative therapeutic strategies to fight chronic inflammation.