Detection of Functional VH81X Heavy Chains in Adult Mice with an Assessment of Complementarity-Determining Region 3 Diversity and Capacity to Form Pre-B Cell Receptor1

Detection of Functional VH81X Heavy Chains in Adult Mice with an Assessment of Complementarity-Determining Region 3 Diversity and Capacity to Form Pre-B Cell Receptor1
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通过评估互补决定区 3 的多样性和形成前 B 细胞受体的能力来检测成年小鼠的功能性 VH81X 重链1

DOI:
10.4049/jimmunol.169.4.1970
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发表时间:
2002
期刊:
The Journal of Immunology
影响因子:
--
通讯作者:
G. H. Kline
G. H. Kline
中科院分区:
--
文献类型:
--
作者:
T. Hayden;P. Riegert;G. H. Kline

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最近的报道表明,所形成的所有H链蛋白中高达50%不能与替代L链复合物结合,因此不能形成前B细胞受体(pBCR),这是等位基因排斥所需的,并且在大多数情况下,证实H链可以与L链组装形成Ab分子。某些VH基因,如VH 81 X,似乎特别倾向于编码非配对(功能障碍)H链。有人认为,互补决定区3的序列变异性,特别是当由酶TdT增加时,通常会排除使用VH 81 X的H链形成pBCR的能力。为了确定是否存在一个基序,该基序解释了H链与替代L链复合物/L链配对的能力,我们培育了一个小鼠系,其中H链重组只能发生在一个等位基因上,使我们能够编译一个H链库,该库能够在不存在功能失调的H链的情况下形成Ab分子。有些出乎意料的是,我们发现VH 81 X H链能够在TdT存在下形成Ab并在细胞表面表达。这些H链的仔细检查已经揭示,虽然高度倾向于编码功能障碍的H链,但序列变异性在功能VH 81 X H链中并不严重受限。我们还证明,表面IG的表达是高度指示的能力的H链形成pBCR。
Recent reports have indicated that up to 50% of all H chain proteins formed cannot associate with the surrogate L chain complex and therefore fail to form a pre-B cell receptor (pBCR), which is required for allelic exclusion and, in most cases, verifies that the H chain can assemble with the L chain to form an Ab molecule. Certain VH genes, such as VH81X, appear to be particularly prone to encoding for nonpairing (dysfunctional) H chains. It has been suggested that sequence variability at complementarity-determining region 3, especially when increased by the enzyme TdT, often precludes the ability of VH81X-using H chains to form pBCR. To determine whether a motif exists that accounts for the ability of H chains to pair with surrogate L chain complex/L chain, we have bred a mouse line in which H chain recombination can only occur on one allele, allowing us to compile a pool of H chains capable of forming Ab molecules in the absence of dysfunctional H chains. Somewhat unexpectedly, we have found VH81X H chains capable of Ab formation and cell surface expression in the presence of TdT. Scrutiny of these H chains has revealed that, although highly prone to encode for dysfunctional H chains, sequence variability is not severely limited among functional VH81X H chains. We also demonstrate that surface Ig expression is highly indicative of the capacity of a H chain to form pBCR.
在前 B 细胞向 B 细胞转变过程中,重链 V 基因特异性消除 B 细胞。
DOI: --
发表时间: 1995
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Decker,DJ;Kline,GH;Hayden,TA;Zaharevitz,SN;Klinman,NR
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DOI: 10.1126/science.8356451
发表时间: 1993-08-27
期刊: SCIENCE
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通讯作者: ALT, FW
DOI: 10.1093/intimm/9.4.493
发表时间: 1997-04-01
影响因子: 4.4
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Martin, F;Chen, XJ;Kearney, JF
通讯作者: Kearney, JF
DOI: 10.1073/pnas.88.14.6284
发表时间: 1991-07
影响因子: 11.1
作者:
N. Nishimoto;H. Kubagawa;T. Ohno;G. Gartland;A. Stanković;Max D. CooPE
通讯作者: N. Nishimoto;H. Kubagawa;T. Ohno;G. Gartland;A. Stanković;Max D. CooPE
VH81X 基因片段非生产性重排的优势证明了 B 细胞克隆成熟对新生 H 链结构的依赖性。
DOI: --
发表时间: 1991
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Decker,DJ;Boyle,NE;Klinman,NR
通讯作者: Klinman,NR