Persistence of functional memory B cells recognizing SARS-CoV-2 variants despite loss of specific IgG
Stephan Winklmeier,
Katharina Eisenhut,
Damla Taskin,
Heike Rübsamen,
Ramona Gerhards,
Celine Schneider,
Paul R. Wratil,
Marcel Stern,
Peter Eichhorn,
Oliver T. Keppler,
Matthias Klein,
Simone Mader,
Tania Kümpfel,
Edgar Meinl
Affiliations
Stephan Winklmeier
Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, 81377 Munich, Germany; Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Martinsried, Germany
Katharina Eisenhut
Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, 81377 Munich, Germany; Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Martinsried, Germany
Damla Taskin
Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, 81377 Munich, Germany; Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Martinsried, Germany
Heike Rübsamen
Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, 81377 Munich, Germany; Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Martinsried, Germany
Ramona Gerhards
Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, 81377 Munich, Germany; Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Martinsried, Germany
Celine Schneider
Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, 81377 Munich, Germany; Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Martinsried, Germany
Paul R. Wratil
Max von Pettenkofer Institute & GeneCenter, Virology, LMU Munich, 80336 Munich, Germany
Marcel Stern
Max von Pettenkofer Institute & GeneCenter, Virology, LMU Munich, 80336 Munich, Germany
Peter Eichhorn
Institute of Laboratory Medicine, University Hospital, LMU Munich, 81377 Munich, Germany
Oliver T. Keppler
Max von Pettenkofer Institute & GeneCenter, Virology, LMU Munich, 80336 Munich, Germany
Matthias Klein
Department of Neurology, University Hospital, LMU Munich, 81377 Munich, Germany
Simone Mader
Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, 81377 Munich, Germany; Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Martinsried, Germany
Tania Kümpfel
Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, 81377 Munich, Germany; Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Martinsried, Germany
Edgar Meinl
Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, 81377 Munich, Germany; Biomedical Center (BMC), Faculty of Medicine, LMU Munich, 82152 Martinsried, Germany; Corresponding author
Summary: Although some COVID-19 patients maintain SARS-CoV-2-specific serum immunoglobulin G (IgG) for more than 6 months postinfection, others eventually lose IgG levels. We assessed the persistence of SARS-CoV-2-specific B cells in 17 patients, 5 of whom had lost specific IgGs after 5–8 months. Differentiation of blood-derived B cells in vitro revealed persistent SARS-CoV-2-specific IgG B cells in all patients, whereas IgA B cells were maintained in 11. Antibodies derived from cultured B cells blocked binding of viral receptor-binding domain (RBD) to the cellular receptor ACE-2, had neutralizing activity to authentic virus, and recognized the RBD of the variant of concern Alpha similarly to the wild type, whereas reactivity to Beta and Gamma were decreased. Thus, differentiation of memory B cells could be more sensitive for detecting previous infection than measuring serum antibodies. Understanding the persistence of SARS-CoV-2-specific B cells even in the absence of specific serum IgG will help to promote long-term immunity.
