期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：22
页码：12295-12305
DOI：10.1073/pnas.1921673117
出版社：The National Academy of Sciences of the United States of America
摘要：The mechanisms that regulate germinal center (GC) B cell responses in the spleen are not fully understood. Here we use a combination of pharmacologic and genetic approaches to delete SIGN-R1 marginal zone (MZ) macrophages and reveal their specific contribution to the regulation of humoral immunity in the spleen. We find that while SIGN-R1 macrophages were not essential for initial activation of B cells, they were required for maturation of the response and development of GC B cells. These defects could be corrected when follicular helper T (Tfh) cells were induced before macrophage ablation or when Tfh responses were enhanced. Moreover, we show that in the absence of SIGN-R1 macrophages, DCIR2 dendritic cells (DCs), which play a key role in priming Tfh responses, were unable to cluster to the interfollicular regions of the spleen and were instead displaced to the MZ. Restoring SIGN-R1 macrophages to the spleen corrected positioning of DCIR2 DCs and rescued the GC B cell response. Our study reveals a previously unappreciated role for SIGN-R1 macrophages in regulation of the GC reaction and highlights the functional specification of macrophage subsets in the MZ compartment.
关键词：marginal zone macrophages ; germinal center B cells ; marginal zone B cells
