IL-17 Promotes Differentiation of Splenic LSK Lymphoid Progenitors into B Cells following Infection.

LineageSca-1c-Kit (LSK) cells are a lymphoid progenitor population that expands in the spleen and preferentially differentiates into mature B cells in response to infection in mice. Furthermore, LSK derived B cells can subsequently contribute to the ongoing immune response through the generation of parasite-specific Ab-secreting cells, as well as germinal center and memory B cells. However, the factors that promote their differentiation into B cells in the spleen postinfection are not defined. In this article, we show that LSK cells produce the cytokine IL-17 in response to infection. Using mice, IL-17R signaling in cells other than LSK cells was found to support their differentiation into B cells. Moreover, primary splenic stromal cells grown in the presence of IL-17 enhanced the production of CXCL12, a chemokine associated with B cell development in the bone marrow, by a population of IL-17RA-expressing podoplaninCD31 stromal cells, a profile associated with fibroblastic reticular cells. Subsequent blockade of CXCL12 in vitro reduced differentiation of LSK cells into B cells, supporting a direct role for this chemokine in this process. Immunofluorescence indicated that podoplanin stromal cells in the red pulp were the primary producers of CXCL12 after infection. Furthermore, podoplanin staining on stromal cells was more diffuse, and CXCL12 staining was dramatically reduced in mice postinfection. Together, these results identify a distinct pathway that supports lymphoid development in the spleen during acute infection.