Origins of serum IgA antibodies

描述（由申请人提供）：我们的目的是确定控制持久伊加应答产生的因素，并确定肠道微生物在促进对肠道抗原和病原体的全身伊加应答中的作用。支撑这项工作的中心假设是，丝状细菌分节段（SF B）通过引发肠道驻留T和B细胞来促进全身性伊加应答，从而增加粘膜伊加+分泌细胞的产生，这些细胞随后在骨髓中定植为长寿浆细胞的小生境。 另外的实验将确定肠道和骨髓中分泌IgA的浆细胞在稳态和对肠道病原体的反应中的寿命。 具体而言，我们将：1）定义SFB定殖对骨髓浆细胞池的影响，2）定义SFB定殖对针对肠道微生物的系统性伊加应答的影响，3）定义LP和BM中伊加+PC的衰减动力学。

DESCRIPTION (provided by applicant): Our intent is to define the factors controlling the generation of lasting IgA responses and determine the role of commensal microbes in promoting systemic IgA responses to enteric antigens and pathogens. The central hypothesis underpinning this work is that Segmented Filamentous Bacteria (SFB) promote systemic IgA responses by priming gut-resident T and B cells, thus augmenting the generation of mucosal IgA+-secreting cells that subsequently colonize niches for long-lived plasma cells in the bone marrow. Additional experiments will define the life span of IgA-secreting plasma cells in the gut and the bone marrow, at steady state and in response to an enteric pathogen. Specifically we will: 1) Define the impact of SFB colonization on the bone marrow plasma cell pool, 2) Define the impact of SFB colonization on systemic IgA responses to enteric microbes, 3) Define decay kinetics for IgA+ PCs in the LP and the BM.