B-1 cells in the bone marrow are a significant source of natural IgM.

B-1 cells in the bone marrow are a significant source of natural IgM.
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DOI:
10.1002/eji.201141890
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发表时间:
2012-01
影响因子:
5.4
通讯作者:
Baumgarth, Nicole
Baumgarth, Nicole
中科院分区:
医学3区
文献类型:
--
作者:
Choi, Youn Soo;Dieter, Jacquelyn A.;Rothaeusler, Kristina;Luo, Zheng;Baumgarth, Nicole

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在没有抗原挑战的情况下分泌的天然IgM抗体是抗微生物免疫和组织稳态的重要贡献者。早期的研究已经确定骨髓和脾脏(在较小程度上)是这种自发分泌IgM的主要组织来源。然而,负责的B细胞亚群从未被确定。利用多色流式细胞术、细胞分选和嵌合小鼠(其中B-1和B-2细胞及其分泌的抗体由其igg异型区分),我们明确地在脾脏中鉴定出天然的IgM分泌细胞,并首次在骨髓中鉴定出IgM+ IgDlo/−CD19hi CD43+ CD5+/−B-1细胞。新发现的骨髓B-1细胞群显示出脾B-1细胞的许多表型特征,但与腹腔B-1细胞不同,腹腔B-1细胞最多只能产生非常少量的IgM。分泌抗体的脾和骨髓B-1细胞也不同于由抗原诱导的常规B细胞产生的终末分化浆细胞,因为它们表达高水平的表面IgM和CD19,而缺乏CD138的表达。总之,该研究确定了脾脏和骨髓中非终末分化的B-1细胞群体是天然IgM的最重要生产者。
Natural IgM antibodies secreted in the absence of antigenic challenge are important contributors to antimicrobial immunity and tissue homeostasis. Early studies had identified bone marrow and, to a lesser extent the spleen, as main tissue sources of this spontaneously secreted IgM. However, the responsible B cell subset has never been identified. Using multicolor flow cytometry, cell sorting and chimeric mice in which B-1 and B-2 cells and their secreted antibodies are distinguished by their Ig-allotype, we unequivocally identify the natural IgM secreting cells in spleen, and for the first time in the bone marrow as IgM+ IgDlo/−CD19hi CD43+ CD5+/− B-1 cells. The newly identified population of bone marrow B-1 cells shows many of the phenotypic characteristics of splenic B-1 cells but is distinct from B-1 cells in the peritoneal cavity, which generate at best very small amounts of IgM. Antibody-secreting spleen and bone marrow B-1 cells are distinct also from terminally differentiated plasma cells generated from antigen-induced conventional B cells, as they express high levels of surface IgM and CD19 and lack expression of CD138. Together the study identifies populations of non-terminally differentiated B-1 cells in spleen and bone marrow as the most significant producers of natural IgM.
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