Lymphotoxin-Dependent B Cell-FRC Crosstalk Promotes De Novo Follicle Formation and Antibody Production following Intestinal Helminth Infection

• Helminth infection drives de novo B cell follicle formation in the draining mLN
• B cells promote FRC proliferation and activation via lymphotoxin-LTβR signaling
• IL-4Rα is necessary for helminth-induced lymphotoxin expression by B cells
• LTβR signaling to FRCs promotes de novo follicle formation and antibody production

SummarySecondary lymphoid tissues provide specialized niches for the initiation of adaptive immune responses and undergo a remarkable expansion in response to inflammatory stimuli. Although the formation of B cell follicles was previously thought to be restricted to the postnatal period, we observed that the draining mesenteric lymph nodes (mLN) of helminth-infected mice form an extensive number of new, centrally located, B cell follicles in response to IL-4Rα-dependent inflammation. IL-4Rα signaling promoted LTα1β2 (lymphotoxin) expression by B cells, which then interacted with CCL19 positive stromal cells to promote lymphoid enlargement and the formation of germinal center containing B cell follicles. Importantly, de novo follicle formation functioned to promote both total and parasite-specific antibody production. These data reveal a role for type 2 inflammation in promoting stromal cell remodeling and de novo follicle formation by promoting B cell-stromal cell crosstalk.

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