Human C. difficile toxin–specific memory B cell repertoires encode poorly neutralizing antibodies

• Main Authors: Hemangi B. Shah, Kenneth Smith, Edgar J. Scott II, Jason L. Larabee, Judith A. James, Jimmy D. Ballard, Mark L. Lang
• Format: Article
• Language: English
• Published: American Society for Clinical investigation 2020-08-01
• Series: JCI Insight
• Subjects: Immunology; Infectious disease
• Online Access: https://doi.org/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.