High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells.
Sci Immunol
; 7(68): eabl5652, 2022 Feb 04.
Article
in English
| MEDLINE | ID: covidwho-1673340
ABSTRACT
T follicular helper (TFH) cells are the conventional drivers of protective, germinal center (GC)based antiviral antibody responses. However, loss of TFH cells and GCs has been observed in patients with severe COVID-19. As T cellB cell interactions and immunoglobulin class switching still occur in these patients, noncanonical pathways of antibody production may be operative during SARS-CoV-2 infection. We found that both TFH-dependent and -independent antibodies were induced against SARS-CoV-2 infection, SARS-CoV-2 vaccination, and influenza A virus infection. Although TFH-independent antibodies to SARS-CoV-2 had evidence of reduced somatic hypermutation, they were still high affinity, durable, and reactive against diverse spike-derived epitopes and were capable of neutralizing both homologous SARS-CoV-2 and the B.1.351 (beta) variant of concern. We found by epitope mapping and B cell receptor sequencing that TFH cells focused the B cell response, and therefore, in the absence of TFH cells, a more diverse clonal repertoire was maintained. These data support an alternative pathway for the induction of B cell responses during viral infection that enables effective, neutralizing antibody production to complement traditional GC-derived antibodies that might compensate for GCs damaged by viral inflammation.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antibodies, Neutralizing
/
T Follicular Helper Cells
/
SARS-CoV-2
/
COVID-19
/
Antibodies, Viral
Topics:
Vaccines
/
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
Sci Immunol
Year:
2022
Document Type:
Article
Affiliation country:
Sciimmunol.abl5652
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