Thymic stromal lymphopoietin can restore functional T cell-independent antibody responses in young mice (150.5)

Abstract

Abstract Unlike adults, young children cannot mount an antibody response to T cell-independent (TI) antigens such as Pneumococcal polysaccharides (PPS) and the basis for this impairment remains elusive. The ontogeny of B cells early in life is IL-7-independent, whereas in adults it is IL-7-dependent. Despite having TI B cell subsets, young wildtype or adult IL-7-/- mice are impaired in anti-PPS response and do not survive Pneumococcal challenge. In contrast, enforced expression of IL-7 restores protective anti-PPS responses in young mice, indicating that IL-7-dependent B cells are critical for TI responses. Thymic stromal lymphopoietin (TSLP) is structurally similar to IL-7 and utilizes IL-7Rα for signaling, therefore it may also contribute to the development of TI B cell responses. Indeed, we found that young TSLP transgenic mice generate an anti-PPS response and protective immunity comparable to that of adult mice. TSLP can be induced upon activation of TLR2 and TLR9. Borrelia hermsii, an agent of relapsing fever, activates TLR2 and TLR9 signaling and induces a protective TI antibody response even in young mice, suggesting that TSLP induced during this infection could play a role in anti-B. hermsii responses. Indeed, IL-7Rα-/- mice (deficient in both IL-7 and TSLP signaling) have a more severe impairment in anti-B.hermsii responses and suffer more prolonged bacteremia than IL-7-/- or TSLPR-/- mice. These data indicate that TSLP can restore functional TI responses in the young.