Kurosu K, Yumoto N, Furukawa M, Kuriyama T, Mikata A
First Department of Pathology, School of Medicine, Chiba University, Chiba City, Japan.
Am J Respir Crit Care Med. 1997 Apr;155(4):1453-60. doi: 10.1164/ajrccm.155.4.9105093.
We analyzed the third complementarity-determining region (CDR3) of the immunoglobulin heavy chain (IgH) gene in five patients with lymphoid interstitial pneumonia (LIP) through a two-step polymerase chain reaction (PCR) and sequencing analysis. By sequencing analysis of the PCR products, morphologic LIP could be divided into two groups: a polyclonal type and a minor monoclonal type. Because of their high frequencies, minor monoclonal clones seemed to be neoplastic clones hidden in normally reactive lymphocyte clones. Consequently, only the polyclonal type might have represented true LIP. Sequencing of the PCR products from open-chest biopsy and transbronchial lung biopsy (TBLB) specimens obtained 8 yr later in one patient with minor monoclonal type LIP confirmed this possibility. In true LIP, six of 20 lymphocyte clones showed 67 to 86% homology with lymphocyte clones derived from fetal tissue. In three of these six clones, the D-region (N-D-N) lengths were very short, whereas four clones showed a high homology with autoreactive lymphocytes (rheumatoid factor, anti-DNA antibody, and G6-positive lymphocytes). Since rheumatoid factors, anti-DNA antibodies, and G6 are autoreactive antibodies, immature B cells stimulated by autoantigens might play some role in the pathogenesis of true LIP.
我们通过两步聚合酶链反应（PCR）和测序分析，对5例淋巴间质性肺炎（LIP）患者免疫球蛋白重链（IgH）基因的第三个互补决定区（CDR3）进行了分析。通过对PCR产物的测序分析，形态学上的LIP可分为两组：多克隆型和少量单克隆型。由于其出现频率较高，少量单克隆克隆似乎是隐藏在正常反应性淋巴细胞克隆中的肿瘤性克隆。因此，可能只有多克隆型代表真正的LIP。对1例少量单克隆型LIP患者8年后获取的开胸活检和经支气管肺活检（TBLB）标本的PCR产物进行测序，证实了这种可能性。在真正的LIP中，20个淋巴细胞克隆中有6个与源自胎儿组织的淋巴细胞克隆显示出67%至86%的同源性。在这6个克隆中的3个中，D区（N-D-N）长度非常短，而4个克隆与自身反应性淋巴细胞（类风湿因子、抗DNA抗体和G6阳性淋巴细胞）显示出高度同源性。由于类风湿因子、抗DNA抗体和G6是自身反应性抗体，由自身抗原刺激的未成熟B细胞可能在真正LIP的发病机制中发挥一定作用。
