Distinct and Overlapping Functions for Thymic Stromal Lymphopoietin‐ and Interleukin 7‐driven B cells in T cell‐independent Antibody Responses

Abstract

T cell independent (TI) responses are impaired in young children but not in adults. B1b cells mount the majority of the TI antibody response to pneumococcal polysaccharide and Borrelia hermsii. Although antigens driving this response have been identified, the developmental origin of the antigen‐specific B1b cells is unknown. Thymic stromal lymphopoietin (TSLP) is responsible for most perinatal B cell development, while interleukin 7 (IL7) plays a crucial role in adult B lymphopoiesis. To determine whether distinct B1b cell development pathways are accountable for the impaired TI responses in young children, we investigated antibody responses to a model TI antigen, NP‐ficoll, as well as to B. hermsii infection in mice deficient in either IL7, the TSLP receptor or IL7Rα, a subunit required for both IL7 and TSLP signaling. TSLPR−/− mice exhibited a normal response to NP‐Ficoll suggesting that IL7‐driven B1b cells constitute the majority of antibody production. However, IL7−/− mice controlled B. hermsii bacteremia as efficiently as TSLPR−/− or wildtype mice suggesting the generation of functionally redundant B1b cells. Indeed, IL7Rα−/− mice were severely impaired in their response to B. hermsii as well as NP‐Ficoll. These data indicate distinct and overlapping roles for IL7‐ and TSLP‐driven B1b cells in TI immunity and suggest that impaired responses in the young are due to an insufficient IL7‐driven B cell response.