Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis

Mice deficient in lymphotoxin beta receptor (LT betaR) or interleukin 7 rec eptor alpha (IL-7R alpha) lack Peyer's patches (PPs). Deficiency in CXC che mokine receptor 5 (CXCR5) also severely affects the development of PPs. A m olecular network involving these three signaling pathways has been implicat ed in PP organogenesis, but it remains unclear how they are connected durin g this process. We have shown that PP organogenesis is initiated at sites c ontaining IL-7R alpha (+):lymphoid cells and vascular cell adhesion molecul e (VCAM)-1/intercellular adhesion molecule (ICAM)-1 expressing nonlymphoid elements. Here we characterize these lymphoid and nonlymphoid components in terms of chemokine signals. The lymphoid population expresses CXCR5 and ha s a strong chemotactic response to B lymphocyte chemoattractant (BLC). Impo rtantly, chemokines produced by VCAM-1(+)ICAM-1(+) nonlymphoid cells mediat e the recruitment of lymphoid cells. Furthermore, we show that these VCAM-1 (+)ICAM-1(+) cells are mesenchymal cells that are activated by lymphoid cel ls through the I;TPR to express adhesion molecules and chemokines. Thus, pr omotion of PP development relies on mutual interaction between mesenchymal and lymphoid cells.