sIgM-FcμR Interactions Regulate Early B Cell Activation and Plasma Cell Development after Influenza Virus Infection.
sIgM-FcμR Interactions Regulate Early B Cell Activation and Plasma Cell Development after Influenza Virus Infection.
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SIGM-FCμR相互作用调节流感病毒感染后的早期B细胞激活和浆细胞发育。
DOI：
10.4049/jimmunol.1700560
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发表时间：
2017-09-01
期刊：
影响因子：
--
通讯作者：
Baumgarth N
中科院分区：
文献类型：
--
作者：
Nguyen TTT;Graf BA;Randall TD;Baumgarth N
以往对μS剪接区(μS−/−)缺失所致的分泌型免疫球蛋白M缺失的小鼠的研究表明，分泌型免疫球蛋白M参与了B细胞的正常发育，并支持最大的抗原特异性免疫球蛋白应答。由于B细胞发育的变化，目前尚不清楚SIGM直接影响B细胞反应的程度和方式。本研究旨在探讨流感病毒感染过程中SIGM介导的免疫球蛋白免疫应答调节的潜在机制。我们用正常发育的μS缺陷B细胞制备小鼠，证明SIGM通过促进早期抗原特异性B细胞的增殖来支持免疫球蛋白应答，而不是通过改变B细胞的发育。B细胞不表达FcμR，但不缺乏Fcα/μR表达或补体活化，其抗病毒免疫应答降低程度与μS−/−小鼠相同。与对照组相比，B细胞特异性Fcmr−/−小鼠在感染后早期缺乏强劲的流感血凝素特异性B细胞的克隆性增殖，并且形成更少的脾和骨髓免疫球蛋白G浆细胞和记忆B细胞。然而，生发中心的反应似乎没有受到影响。SIGM的提供挽救了μS−/−的浆细胞发育，但不能挽救Fcmr−/−B细胞的发育，正如在混合骨髓嵌合小鼠中所证明的那样。综上所述，这些数据表明，SIGM与B细胞上的FcμR相互作用，支持B细胞的早期激活和长期体液免疫的发展。
Previous studies with mice lacking secreted IgM (sIgM) due to a deletion of the μs splice region (μs−/−) had shown sIgM involvement in normal B cell development and in support of maximal antigen-specific IgG responses. Because of the changes to B cell development, it remains unclear to which extent and how sIgM directly affects B cell responses. Here we aimed to explore the underlying mechanisms of sIgM-mediated IgG response regulation during influenza virus infection. Generating mice with normally developed μs-deficient B cells we demonstrate that sIgM supports IgG responses by enhancing early antigen-specific B cell expansion, not by altering B cell development. Lack of FcμR expression on B cells, but not lack of Fcα/μR expression or complement activation, reduced antiviral IgG responses to the same extent as observed in μs−/− mice. B-cell-specific Fcmr−/− mice lacked robust clonal expansion of influenza hemagglutinin-specific B cells early after infection and developed fewer spleen and bone marrow IgG plasma cells and memory B cells, compared to controls. However, germinal center responses appeared unaffected. Provision of sIgM rescued plasma cell development from μs−/− but not Fcmr−/− B cells, as demonstrated with mixed bone marrow chimeric mice. Together the data suggest that sIgM interacts with FcμR on B cells to support early B cell activation and the development of long-lived humoral immunity.
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影响因子：
5.4
作者：
Jayasekera, Jerome P.;Moseman, E. Ashley;Carroll, Michael C.
通讯作者：
Carroll, Michael C.
DOI：
10.1084/jem.20080979
发表时间：
2008-12-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Choi YS;Baumgarth N
通讯作者：
Baumgarth N
影响因子：
4.4
作者：
Alugupalli, KR;Gerstein, RM;Leong, JM
通讯作者：
Leong, JM
影响因子：
3.1
作者：
Elsner, Rebecca A.;Hastey, Christine J.;Baumgarth, Nicole
通讯作者：
Baumgarth, Nicole
影响因子：
15.3
作者：
Baumgarth, N;Herman, O C;Jager, G C;Brown, L E;Herzenberg, L A;Chen, J
通讯作者：
Chen, J