Analysis of the role of IL-21 in development of murine B cell progenitors in the bone marrow.
Analysis of the role of IL-21 in development of murine B cell progenitors in the bone marrow.
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DOI：
10.4049/jimmunol.1004040
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发表时间：
2011-05-01
期刊：
影响因子：
--
通讯作者：
Paige CJ
中科院分区：
文献类型：
--
作者：
Simard N;Konforte D;Tran AH;Esufali J;Leonard WJ;Paige CJ
白细胞介素-21（IL-21）在B细胞发育的后期起关键作用，其中已显示其诱导成熟B细胞生长和分化为Ig分泌浆细胞。由于IL-21受体（IL-21 R）也已被报道在骨髓（BM）B细胞祖细胞，我们调查是否IL-21 R影响早期阶段的B细胞的发展。IL-21 R早在proB细胞阶段就有功能，并且受体介导的信号传导的强度随着细胞成熟而增加。向细胞培养物中的B祖细胞中添加IL-21导致成熟B细胞标志物的加速出现，并且与Aid、Blimp 1和生殖系转录物（GLT）的诱导相关。我们还发现IL-21 R和CD 40的刺激足以诱导早期B祖细胞成熟为IgM和IgG分泌细胞。与IL-21促进B细胞分化的作用一致，在IL-21 R缺陷小鼠（ILR-21−/−）的BM中，B220+ CD 43 +IgM− proB细胞的数量增加，成熟IgMhiIgDhi细胞的数量减少。我们还报道了IL-21由BM CD 4 + T细胞表达。这些结果提供了IL-21 R在B细胞祖细胞中起作用的第一个证据，并表明IL-21调节B细胞发育。
Interleukin-21 (IL-21) plays a key role in the late stage of B cell development, where it has been shown to induce growth and differentiation of mature B cells into Ig-secreting plasma cells. Since IL-21 receptors (IL-21R) have also been reported on bone marrow (BM) B cell progenitors, we investigated whether IL-21R influenced earlier stages of B cell development. IL-21R is functional as early as the proB cell stage and the strength of receptor-mediated signalling increases as cells mature. The addition of IL-21 to B cell progenitors in cell culture resulted in the accelerated appearance of mature B cell markers and was associated with the induction of Aid, Blimp1, and germline transcripts (GLTs). We also found that stimulation of both IL-21R and CD40 was sufficient to induce the maturation of early B cell progenitors into IgM- and IgG-secreting cells. Consistent with a role for IL-21 in promoting B cell differentiation, the number of B220+CD43+IgM− proB cells was increased and the number of mature IgMhiIgDhi cells was decreased in BM of IL-21R-deficient mice (ILR-21−/−). We also report here that IL-21 is expressed by BM CD4+ T cells. These results provide the first evidence that IL-21R is functional in B cell progenitors and indicate that IL-21 regulates B cell development.
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DOI：
10.1084/jem.20081571
发表时间：
2009-01-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dienz O;Eaton SM;Bond JP;Neveu W;Moquin D;Noubade R;Briso EM;Charland C;Leonard WJ;Ciliberto G;Teuscher C;Haynes L;Rincon M
通讯作者：
Rincon M
影响因子：
20.3
作者：
Cariappa, Annaiah;Chase, Catharine;Pillai, Shiv
通讯作者：
Pillai, Shiv
影响因子：
20.3
作者：
Lindsley, Robert Coleman;Thomas, Matthew;Allman, David
通讯作者：
Allman, David
影响因子：
20.3
作者：
Cassese, Giuliana;Parretta, Elisabetta;Di Rosa, Francesca
通讯作者：
Di Rosa, Francesca
DOI：
10.1073/pnas.0807309106
发表时间：
2009-02-03
影响因子：
11.1
作者：
Bubier, Jason A.;Sproule, Thomas J.;Roopenian, Derry C.
通讯作者：
Roopenian, Derry C.