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Human C. difficile toxin–specific memory B cell repertoires encode poorly neutralizing antibodies
Hemangi B. Shah, … , Jimmy D. Ballard, Mark L. Lang
Hemangi B. Shah, … , Jimmy D. Ballard, Mark L. Lang
Published July 14, 2020
Citation Information: JCI Insight. 2020;5(16):e138137. https://doi.org/10.1172/jci.insight.138137.
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Research Article Immunology Infectious disease

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

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Abstract

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.

Authors

Hemangi B. Shah, Kenneth Smith, Edgar J. Scott II, Jason L. Larabee, Judith A. James, Jimmy D. Ballard, Mark L. Lang

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