Chrisment Delphine, Dubus Pierre, Chambonnier Lucie, Hocès de la Guardia Anaïs, Sifré Elodie, Giese Alban, Capone Myriam, Khairallah Camille, Costet Pierre, Rousseau Benoît, Hubert Christophe, Burlen-Defranoux Odile, Varon Christine, Bandeira Antonio, Mégraud Francis, Lehours Philippe
Bacteriology Laboratory, University of Bordeaux, Bordeaux, France; INSERM U853, Bordeaux, France.
EA 2406, University of Bordeaux, Bordeaux, France.
Am J Pathol. 2014 Aug;184(8):2174-84. doi: 10.1016/j.ajpath.2014.04.008. Epub 2014 Jun 6.
Neonatal thymectomy in BALB/c mice has been described as a model of gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML). By using this experimental system, we screened, for the first time to our knowledge, Helicobacter pylori GML-associated strains for their capacity to promote disease. A cohort of BALB/c mice underwent thymectomy at day 3 after birth (d3Tx). Successful thymic ablation was evaluated by the degree of lymphopenia in blood samples collected at 4 weeks of age. d3Tx and non-thymectomized controls were infected with either GML strains (B38 or B47) or control strains (SS1 or TN2GF4). Gastric samples collected at 6, 12, and 18 months after infection were studied for bacteria content, and submitted to histological, immunochemical, molecular, and immunological analyses. Severe gastric inflammation was only observed in d3Tx mice. In these animals, the gastric lamina propria was infiltrated with lymphoid cells organized in follicles composed of B cells with few infiltrating T cells. PCR of D/J IgH gene segments proved the monoclonality of infiltrating B cells, which strongly correlated with the presence of lymphoepithelial lesions. B-cell infiltrates were particularly prominent in mice infected with the B47-GML strain. No pathological changes were detected in noninfected d3Tx mice. We identified new H. pylori isolates adapted to the mouse stomach with high potential of GML development, which is only revealed in hosts rendered lymphopenic by neonatal thymic ablation.
在BALB/c小鼠中进行新生期胸腺切除术已被描述为胃黏膜相关淋巴组织（MALT）淋巴瘤（GML）的一种模型。利用这个实验系统，据我们所知，我们首次筛选了与幽门螺杆菌GML相关的菌株促进疾病的能力。一组BALB/c小鼠在出生后第3天（d3Tx）接受胸腺切除术。通过对4周龄时采集的血样中的淋巴细胞减少程度来评估胸腺切除是否成功。d3Tx组和未进行胸腺切除的对照组分别感染GML菌株（B38或B47）或对照菌株（SS1或TN2GF4）。对感染后6个月、12个月和18个月采集的胃样本进行细菌含量研究，并进行组织学、免疫化学、分子和免疫学分析。仅在d3Tx小鼠中观察到严重的胃炎症。在这些动物中，胃固有层被淋巴细胞浸润，这些淋巴细胞组织成由B细胞组成的滤泡，仅有少量浸润的T细胞。D/J IgH基因片段的PCR证明浸润的B细胞具有单克隆性，这与淋巴上皮病变的存在密切相关。B细胞浸润在感染B47 - GML菌株的小鼠中尤为突出。未感染的d3Tx小鼠未检测到病理变化。我们鉴定出了适应小鼠胃且具有很高GML发展潜力的新型幽门螺杆菌分离株，这种潜力仅在因新生期胸腺切除而导致淋巴细胞减少的宿主中才显现出来。
