IL-17 Promotes Differentiation of Splenic LSK− Lymphoid Progenitors into B Cells following Plasmodium yoelii Infection

Abstract

<p class="first" id="P1">LSK ⁻ (Lineage ⁻Sca-1 ⁺c-kit ⁻) cells are a lymphoid progenitor population that expands in the spleen and preferentially differentiates into mature B cells in response to <i>Plasmodium yoelii</i> infection in mice. Furthermore, LSK ⁻ derived B cells can subsequently contribute to the ongoing immune response through the generation of parasite-specific antibody secreting cells, and germinal center and memory B cells. However, the factors that promote their differentiation into B cells in the spleen after infection are not defined. Here we show that LSK ⁻ cells produce the cytokine IL-17 in response to <i>Plasmodium</i> infection. Using <i>Il-17ra</i> ^−/− 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 podoplanin ⁺CD31 ⁻ stromal cells, a profile associated with fibroblastic reticular cells. Subsequent blockade of CXCL12 <i>in vitro</i> 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 <i>P. yoelii</i> infection. Furthermore, podoplanin staining on stromal cells was more diffuse, and CXCL12 staining was dramatically reduced in <i>Il-17ra</i> ^−/− mice after infection. Together these results identify a distinct pathway that supports lymphoid development in the spleen during acute <i>Plasmodium</i> infection. </p>