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在健康个体中,类别转换为IgD的成熟B细胞具有自身反应性。

Mature B cells class switched to IgD are autoreactive in healthy individuals.

作者信息

Koelsch Kristi, Zheng Nai-Ying, Zhang Qingzhao, Duty Andrew, Helms Christina, Mathias Melissa D, Jared Mathew, Smith Kenneth, Capra J Donald, Wilson Patrick C

机构信息

Molecular Immunogenetics Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.

出版信息

J Clin Invest. 2007 Jun;117(6):1558-65. doi: 10.1172/JCI27628. Epub 2007 May 17.

Abstract

Determination of the origin and fate of autoreactive B cells is critical to understanding and treating autoimmune diseases. We report that, despite being derived from healthy people, antibodies from B cells that have class switched to IgD via genetic recombination (and thus become class switched to C delta [C delta-CS] cells) are highly reactive to self antigens. Over half of the antibodies from C delta-CS B cells bind autoantigens on human epithelioma cell line 2 (HEp-2) cells or antinuclear antigens, and a quarter bind double-stranded DNA; both groups of antibodies are frequently polyreactive. Intriguingly, some C delta-CS B cells have accumulated basic residues in the antibody variable regions that mediate anti-DNA reactivity via somatic hypermutation and selection, while other C delta-CS B cells are naturally autoreactive. Though the total percentage was appreciably less than for C delta-CS cells, a surprising 31% of IgG memory cell antibodies were somewhat autoreactive, and as expected, about 24% of naive cell antibodies were autoreactive. We interpret these findings to indicate either that autoreactive B cells can be induced to class switch to IgD or that autoreactive B cells that use IgD as the B cell receptor are not effectively deleted. Determination of the mechanism by which the majority of C delta-CS B cells are autoreactive may be important in understanding peripheral tolerance mechanisms and may provide insight into the enigmatic function of the IgD antibody.

摘要

确定自身反应性B细胞的起源和命运对于理解和治疗自身免疫性疾病至关重要。我们报告称,尽管来自健康个体,但通过基因重组已类别转换为IgD(从而成为类别转换为Cδ[Cδ-CS]细胞)的B细胞所产生的抗体对自身抗原具有高度反应性。超过一半的来自Cδ-CS B细胞的抗体与人上皮瘤细胞系2(HEp-2)细胞上的自身抗原或抗核抗原结合,四分之一的抗体与双链DNA结合;这两组抗体通常具有多反应性。有趣的是,一些Cδ-CS B细胞在抗体可变区积累了碱性残基,这些残基通过体细胞超突变和选择介导抗DNA反应性,而其他Cδ-CS B细胞则天然具有自身反应性。尽管总百分比明显低于Cδ-CS细胞,但令人惊讶的是,31%的IgG记忆细胞抗体有一定程度的自身反应性,正如预期的那样,约24%的幼稚细胞抗体具有自身反应性。我们对这些发现的解释是,要么自身反应性B细胞可被诱导类别转换为IgD,要么以IgD作为B细胞受体的自身反应性B细胞未被有效清除。确定大多数Cδ-CS B细胞具有自身反应性的机制可能对理解外周耐受机制很重要,并可能为IgD抗体的神秘功能提供见解。

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本文引用的文献

1
Autoreactivity in human IgG+ memory B cells.
Immunity. 2007 Feb;26(2):205-13. doi: 10.1016/j.immuni.2007.01.009.
2
The riddle of the dual expression of IgM and IgD.
Immunology. 2006 Aug;118(4):429-37. doi: 10.1111/j.1365-2567.2006.02386.x.
3
A checkpoint for autoreactivity in human IgM+ memory B cell development.
J Exp Med. 2006 Feb 20;203(2):393-400. doi: 10.1084/jem.20052033. Epub 2006 Jan 30.
4
Early preplasma cells define a tolerance checkpoint for autoreactive B cells.
J Immunol. 2006 Jan 15;176(2):790-802. doi: 10.4049/jimmunol.176.2.790.
5
The evolution of human anti-double-stranded DNA autoantibodies.
Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9258-63. doi: 10.1073/pnas.0500132102. Epub 2005 Jun 20.
8
Intricacies of anti-DNA autoantibodies.
J Immunol. 2004 Mar 15;172(6):3367; author reply 3367-8. doi: 10.4049/jimmunol.172.6.3367.
9
Surrogate light chain expressing human peripheral B cells produce self-reactive antibodies.
J Exp Med. 2004 Jan 5;199(1):145-50. doi: 10.1084/jem.20031550. Epub 2003 Dec 29.
10
Predominant autoantibody production by early human B cell precursors.
Science. 2003 Sep 5;301(5638):1374-7. doi: 10.1126/science.1086907. Epub 2003 Aug 14.

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