CCL19-Cre transgenics: targeting lymph node fibroblastic reticular cells in vivo (44.14)

Abstract The paracortex of lymph nodes (LNs) harbors a sponge-like scaffold of stromal cells known as fibroblastic reticular cells (FRCs). A major function of FRCs is to build and enwrap the conduit system of collagen fibers that directs interstitial fluids from the afferent lymph through the T-cell zone to HEVs. Furthermore, FRCs regulate T-cell migration and survival by producing the chemokines CCL19 and CCL21. To gain further knowledge on the biology of FRCs and possibly other stromal cell subsets, we have generated a bacterial artificial chromosome (BAC)-transgenic mouse model that utilizes the CCL19 promoter to direct the Cre-recombinase to LN stromal cells. Crossing of CCL19-Cre mice to the R26-EYFP reporter revealed that transgene expression in LNs was almost exclusively confined to podoplanin+CD31- cells. Likewise, transgene activity in spleens and Peyer’s patches of CCL19-Cre mice was largely restricted to FRC-like cells, i.e. stromal cells within the T cell zone and the T-B border. Selective ablation of the lymphotoxin-beta receptor on CCL19-Cre-positive cells resulted in profound changes in the development and organization of secondary lymphoid organs. Taken together, stromal CCL19-Cre expression is well-suited (i) to characterize the development of LN FRCs in vivo, (ii) to molecularly dissect the contribution of stromal cells to lymphoid organogenesis, and (iii) to address the function of LN FRCs in the generation of innate and adaptive immune responses.