Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center (OUHSC).
Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, and.
JCI Insight. 2020 Aug 20;5(16):138137. doi: 10.1172/jci.insight.138137.
Clostridioides difficile is a leading cause of nosocomial infection responsible for significant morbidity and mortality with limited options for therapy. Secreted C. difficile toxin B (TcdB) is a major contributor to disease pathology, and select TcdB-specific Abs may protect against disease recurrence. However, the high frequency of recurrence suggests that the memory B cell response, essential for new Ab production following C. difficile reexposure, is insufficient. We therefore isolated TcdB-specific memory B cells from individuals with a history of C. difficile infection and performed single-cell deep sequencing of their Ab genes. Herein, we report that TcdB-specific memory B cell-encoded antibodies showed somatic hypermutation but displayed limited isotype class switch. Memory B cell-encoded mAb generated from the gene sequences revealed low to moderate affinity for TcdB and a limited ability to neutralize TcdB. These findings indicate that memory B cells are an important factor in C. difficile disease recurrence.
艰难梭菌是导致医院感染的主要原因，其发病率和死亡率较高，治疗选择有限。分泌的艰难梭菌毒素 B（TcdB）是疾病发病机制的主要贡献者，选择 TcdB 特异性 Abs 可能有助于预防疾病复发。然而，高复发率表明，记忆 B 细胞反应对于艰难梭菌再次暴露后新 Ab 的产生是不足的。因此，我们从有艰难梭菌感染史的个体中分离出 TcdB 特异性记忆 B 细胞，并对其 Ab 基因进行单细胞深度测序。在此，我们报告 TcdB 特异性记忆 B 细胞编码的抗体显示体细胞超突变，但显示有限的同种型转换。从基因序列生成的记忆 B 细胞编码的 mAb 对 TcdB 的亲和力低至中等，中和 TcdB 的能力有限。这些发现表明，记忆 B 细胞是艰难梭菌病复发的一个重要因素。
