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
en En
| MEDLINE
| ID: mdl-34914544
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Anticuerpos Neutralizantes
/
Células T Auxiliares Foliculares
/
SARS-CoV-2
/
COVID-19
/
Anticuerpos Antivirales
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Immunol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos