Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the pandemic human respiratory illness COVID-19, is a global health emergency. While severe acute disease has been linked to an expansion of antibody-secreting plasmablasts, we sought to identify B cell responses that correlated with positive clinical outcomes in convalescent patients. We characterized the peripheral blood B cell immunophenotype and plasma antibody responses in 40 recovered non-hospitalized COVID-19 subjects that were enrolled as donors in a convalescent plasma treatment study. We observed a significant negative correlation between the frequency of peripheral blood memory B cells and the duration of symptoms for convalescent subjects. Memory B cell subsets in convalescent subjects were composed of classical CD24+ class-switched memory B cells, but also activated CD24-negative and natural unswitched CD27+ IgD+ IgM+ subsets. Memory B cell frequency was significantly correlated with both IgG1 and IgM responses to the SARS-CoV-2 spike protein receptor binding domain (RBD). IgM+ memory, but not switched memory, directly correlated with virus-specific antibody responses, and remained stable over time. Our findings suggest that the frequency of memory B cells is a critical indicator of disease resolution, and that IgM+ memory B cells play an important role in SARS-CoV-2 immunity.

Understanding the implications of SARS-CoV-2 re-infections on immune response milieu, laboratory tests and control measures against COVID-19

“…A new study discovered that higher number of memory B cells may indicate an efficacious response to an acute infection and aid in understanding T cell response. Both switched and unswitched memory B cells are associated with a shorter length of symptoms [ 56 ]. The degree of IgM + memory is highly associated with anti-RBD IgG1 antibody response.…”

“…The degree of IgM + memory is highly associated with anti-RBD IgG1 antibody response. Hence, it seems like some COVID-19 patients do present a memory response that is protective, either before or after the production of the IgM + memory cells [ 56 ].…”

“…One justification may be that they are not a crucial aspect of recovery, but are limited to acute and chronic viral infection. This part will require additional studies to explain the processes involved [ 56 , 57 , 58 , 59 ]. Alternative explanation for the increased convalescent rates with higher amount of memory B cells is that these cells form part of a bigger pool, resulting to better T cell facilitation of B cell germinal center responses in unexposed individuals during primary infection.…”

“…Alternative explanation for the increased convalescent rates with higher amount of memory B cells is that these cells form part of a bigger pool, resulting to better T cell facilitation of B cell germinal center responses in unexposed individuals during primary infection. This elucidation is plausible since memory production is strictly connected to the production of specific antibodies against the responsible agent [ 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ].…”

Reaktionsmuster der lokoregionären Lymphknoten im Abflussgebiet von COVID-19-Lungen

“…Ein Defekt in CD40LG resultiert in einem Fehlen des Ig-Klassenwechsels, was die präferenzielle extrafollikuläre Proliferation von B‑Zellen begünstigen könnte. Als Abbild der erwähnten 2 Besonderheiten konnte in detaillierten Analysen eine negative Korrelation zwischen der Menge von B‑Gedächtniszellen und der COVID-19-Symptomdauer gezeigt werden [ 33 ]. Die Menge dieser Zellen korrelierte mit IgG1 und IgM gegen das SARS-CoV-2-Spikeprotein.…”