A chemokine-driven positive feedback loop organizes lymphoid follicles

Lymphoid follicles are B-cell-rich compartments of lymphoid organs that fun ction as sites of B-cell antigen encounter and differentiation. CXC chemoki ne receptor-5 (CXCR5) is required for B-cell migration to splenic follicles (1), but the requirements for homing to B-cell areas in lymph nodes remain to be defined. Here we show that lymph nodes contain two types of B-cell-ri ch compartment: follicles containing follicular dendritic cells, and areas lacking such cells. Using gene-targeted mice, we establish that B-lymphocyt e chemoattractant (BLC/BCA1)(2,3) and its receptor, CXCR5, are needed for B -cell homing to follicles in lymph nodes as well as in spleen. We also rnd that BLC is required for the development of most lymph nodes and Peyer's pa tches. In addition to mediating chemoattraction, BLC induces B cells to upr egulate membrane lymphotoxin alpha 1 beta 2, a cytokine that promotes folli cular dendritic cell development and BLC expression(4,5), establishing a po sitive feedback loop that is likely to be important in follicle development and homeostasis. In germinal centres the feedback loop is overridden, with B-cell lymphotoxin a1b2 expression being induced by a mechanism independen t of BLC.