When do microbes stimulate rheumatoid factor?
When do microbes stimulate rheumatoid factor?
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DOI：
10.1084/jem.185.10.1721
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发表时间：
1997-05-19
影响因子：
15.3
通讯作者：
Edinger, J
中科院分区：
文献类型：
--
作者：
Posnett, DN;Edinger, J
抗球蛋白或类风湿因子(RF)在20世纪40年代初首次被描述。它们存在于70%的类风湿性关节炎(RA)患者中，高滴度与严重疾病有关，但也出现在大量其他疾病中，包括病毒、细菌和寄生虫感染(1)。尽管它们广泛存在，但射频是如何或为什么产生的仍然是一个谜。射频有两个变种。低亲和力RF(Kd为105M)是一种IgM天然抗体，对Ig G-Fc决定簇具有特异性，并与其他自身抗原发生交叉反应，即多反应性。它们是由正常人的CD5B细胞产生的。它们通常是免疫球蛋白M抗体，并使用选定的种系V基因来连接H链和L链。这就是为什么它们具有交叉反应的独特型，这是昆克尔等人发现的。20世纪70年代(3)。这些抗体通常不依赖于T细胞。它们类似于EBV(4)或LPS(5，6)对多克隆B细胞激活所产生的RF。产生这些RF的B细胞似乎对恶性转化很敏感，因为RF相关的V基因在低度慢性B淋巴细胞增生性疾病中经常表达，如慢性淋巴细胞白血病、Waldenstrom巨球蛋白血症、混合性冷球蛋白血症和与Sjögren病相关的淋巴瘤。这可能是由于STAT3在B1细胞中的结构性表达(7)。与RF相关的V基因也被人类胎儿B细胞(8，9)过度表达，这可能与低亲和力RF在缺乏成熟体液免疫系统的新生儿中的作用一致。尽管亲和力低，但IgM RF的多价性使乳胶颗粒或红细胞，以及体内包裹着特定抗体的微生物有很好的凝集能力。IgM RF的存在可导致大的免疫复合物形成晶格，难以溶解并被单核巨噬细胞系统迅速清除。高亲和力RF(Kd107M)可以是IgM、Ig G、Ig A或Ig E抗体。类风湿关节炎患者可能具有高滴度的这种类型的RF。它们的产生依赖于T细胞。这些抗体通常不共享低亲和力RF使用的V基因(11)。由于V基因中存在多个体细胞突变，它们已经经历了亲和力成熟，因此由抗原驱动的B细胞产生。这些RF最强烈地与刺激其产生的Ig同型结合。类风湿关节炎滑膜组织中RF含量尤其丰富。在一些报道中，滑膜RF的主要特异性是对IgG3-Fc(12)，这意味着
Anti–-globulins or rheumatoid factors (RF) were first described in the early 1940s. They are present in 70% of patients with rheumatoid arthritis (RA) and high titers are associated with severe disease, but they also appear in a large number of other diseases including viral, bacterial, and parasitic infections (1). In spite of their wide spread occurrence, it is still a puzzle how or why RF are generated. RF come in two varieties. Low affinity RF (Kd of 10 5 M) are IgM natural antibodies with specificity for IgG-Fc determinants and cross-reactivity with other autoantigens, ie, polyreactivity. They are produced by CD5 B cells in normal subjects (2). Frequently they are IgM antibodies and use selected germline V genes for both H and L chains. This is why they share cross-reactive idiotypes, as discovered by Kunkel et al. in the 1970s (3). These antibodies are typically T cell independent. They are similar to the RF produced in response to polyclonal B cell activation by EBV (4) or LPS (5, 6). B cells producing these RF appear to be susceptible to malignant transformation as the RF-associated V genes are frequently expressed in low grade chronic B lymphoproliferative diseases such as chronic lymphocytic leukemia, Waldenstrom’s macroglobulinemia, mixed cryoglobulinemia and lymphoma associated with Sjögren’s disease. This may be due to constitutive expression of STAT3 in B1 cells (7). The RF-associated V genes are also over-expressed by human fetal B cells (8, 9), perhaps consistent with a role for low affinity RF in neonates that lack a mature humoral immune system. In spite of the low affinity, the multivalency of IgM RF allows excellent agglutination of latex particles or red blood cells, and presumably also microbial organisms, in vivo, that are coated with specific IgG antibodies. The presence of IgM RF can lead to large immune complexes with lattice formation, that are poorly soluble and rapidly removed by the mononuclear phagocyte system (10).High affinity RF (Kd of 10 7 M) can be IgM, IgG, IgA, or IgE antibodies. RA patients may have high titers of this type of RF. Their production is T cell dependent. These antibodies often do not share the V genes used by the low affinity RF (11). They have undergone affinity maturation, as there are multiple somatic mutations in the V genes, and are therefore produced by antigen driven B cells. These RF bind most avidly to the Ig isotype which stimulated their production. In RA, RF are particularly abundant in the synovium. In some reports the dominant specificity of synovial RF is for IgG3-Fc (12), implying that the
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T细胞对慢性类风湿关节炎中爱泼斯坦 - 巴尔病毒反式激活剂的反应。
DOI：
10.1084/jem.184.5.1791
发表时间：
1996-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1016/s0167-5699(96)10066-9
发表时间：
1996-12-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
Bachmann, MF;Zinkernagel, RM
通讯作者：
Zinkernagel, RM
影响因子：
15.3
作者：
NEMAZEE, DA
通讯作者：
NEMAZEE, DA
影响因子：
--
作者：
MANNIK, M
通讯作者：
MANNIK, M
影响因子：
56.9
作者：
SCHROEDER, HW;HILLSON, JL;PERLMUTTER, RM
通讯作者：
PERLMUTTER, RM