Activation-induced cytidine deaminase expression and activity in the absence of germinal centers: insights into hyper-IgM syndrome.
Activation-induced cytidine deaminase expression and activity in the absence of germinal centers: insights into hyper-IgM syndrome.
复制标题
DOI：
10.4049/jimmunol.0901548
复制
发表时间：
2009-09-01
期刊：
影响因子：
--
通讯作者：
Ueda Y
中科院分区：
文献类型：
--
作者：
Kuraoka M;Liao D;Yang K;Allgood SD;Levesque MC;Kelsoe G;Ueda Y
体细胞超突变（SHM）通常是在T细胞依赖性（Td）生发中心（GC）应答期间由抗原活化的成熟B细胞表达活化诱导的胞苷脱氨酶（AID）的结果。尽管如此，尽管他们不能表达CD 154和启动GC应答，I型高IgM综合征（HIGM 1）患者支持表达突变的IG基因的IgM+IgD+ CD 27 + B细胞群体。这些突变的B细胞的起源尚不清楚; IgM+IgD+ CD 27+细胞不表达AID，并且似乎获得了不依赖于Ag严格选择的突变。在这里，我们证明了来自CD 154缺陷小鼠骨髓的未成熟/过渡1（im/T1）B细胞表达AID并获得IG突变，这些突变缺乏通过BCR信号传导进行抗原选择的标志。在从鼠胎肝回收的发育不成熟的B细胞和从脐带血回收的人im/T1 B细胞中发现了相当水平的AID表达。AID在人胎肝中的表达也很强，接近人扁桃体组织和人GC B细胞系拉莫斯的表达。这些观察结果使我们得出结论，在发展中的人类B细胞中的AID表达是突变的IgM+IgD+ CD 27 + B细胞存在于HIGM 1患者的起源，我们提出，小鼠和人类共享一个潜在的，艾滋病依赖性途径的免疫前多样化的B淋巴细胞，这是更突出的鸡，羊，兔。
Somatic hypermutation (SHM) normally occurs as a consequence of the expression of activation-induced cytidine deaminase (AID) by antigen-activated, mature B cells during T cell-dependent (Td) germinal center (GC) responses. Nonetheless, despite their inability to express CD154 and initiate GC responses, patients with type-I hyper IgM syndrome (HIGM1), support populations of IgM+IgD+CD27+ B cells that express mutated Ig genes. The origin of these mutated B cells is unknown; the IgM+IgD+CD27+ cells do not express AID and appear to acquire mutations independent of stringent selection by Ag. Here we demonstrate that immature/transitional 1 (im/T1) B cells from the bone marrow of CD154 deficient mice express AID and acquire Ig mutations that lack the hallmarks of antigenic selection via BCR signaling. Comparable levels of AID expression was found in developmentally immature B cells recovered from murine fetal liver and from human im/T1 B cells recovered from umbilical cord blood. AID expression in human fetal liver was also robust, approaching that of human tonsil tissue and the human GC B cell line, Ramos. These observations lead us to conclude that AID expression in developing human B cells is the origin of the mutated IgM+IgD+CD27+ B cells present in HIGM1 patients and we propose that both mice and human share a latent, AID-dependent pathway for the pre-immune diversification of B lymphocytes that is more prominent in chicken, sheep, and rabbits.
登录
查看更多内容
影响因子：
64.5
作者：
BEREK, C;BERGER, A;APEL, M
通讯作者：
APEL, M
影响因子：
15.3
作者：
Foy, Teresa M.;Laman, Jon D.;Ledbetter, Jeffrey A.;Aruffo, Alejandro;Claassen, Eric;Noelle, Randolph J.
通讯作者：
Noelle, Randolph J.
影响因子：
15.3
作者：
Gartner, F;Alt, F W;Monroe, R J;Seidl, K J
通讯作者：
Seidl, K J
DOI：
10.1084/jem.178.5.1567
发表时间：
1993-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Foy TM;Shepherd DM;Durie FH;Aruffo A;Ledbetter JA;Noelle RJ
通讯作者：
Noelle RJ
影响因子：
56.9
作者：
Fagarasan, S;Muramatsu, M;Honjo, T
通讯作者：
Honjo, T