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Pre-existing antibody allows for maturation of new B cells in ‘recall’ germinal centres

Nature Reviews Immunology volume 24, page 234 (2024)Cite this article

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Re-exposure to antigen elicits a robust antibody response in serum, as well as inducing the formation of new ‘recall’ germinal centres (GCs) in lymphoid tissue. The serum antibody response observed after antigen re-exposure is mainly driven by memory B cells, whereas the newly formed recall GCs are almost entirely composed of naive B cells. ‘Recall immunization’ is thus specifically associated with an antibody response mediated by memory B cells that had been generated during the primary antigen encounter, as well as a de novo GC response. This may counteract the phenomenon of ‘original antigenic sin’, in which the antibody response to a previously encountered pathogen can impair subsequent responses to closely related pathogens. However, the mechanisms that facilitate the selective use of ‘primary-derived’ memory B cells for antibody production and the selective recruitment of naive B cells to recall GCs are not well understood.

In a recent preprint (not peer-reviewed), Schiepers et al. show that the seemingly divergent antibody and GC responses observed in recall immunization are linked to antibody-mediated feedback regulation. The authors immunized mice with recombinant haemagglutinin in the right hind footpad, and boosted these mice in the contralateral footpad with the same antigen 1 month later. They found that B cells recruited to the recall GCs did not detectably bind antigen and were thus unable to contribute to antibody titres. The authors hypothesized that pre-existing antibodies were suppressing the ability of B cells with antigen-binding capacity from entering recall GCs. To test this, they ablated plasma cell precursors in the primary GCs to deplete circulating antibodies before homologous boosting. This significantly increased antigen binding in the new recall GCs. Boosting with variant antigens also increased antigen binding in recall GCs, which suggests that antibody feedback steers recall GC B cells towards variant epitopes.

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Original article

Related articles

  • Schiepers, A. et al. Molecular fate-mapping of serum antibody responses to repeat immunization. Nature 615, 482–489 (2023)

  • Mesin, L. et al. Restricted clonality and limited germinal center reentry characterize memory B cell reactivation by boosting. Cell 180, 92–106.e11 (2020)

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  1. OxMS Preprint Journal Club, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Jake Herb & Maria Curotto de Lafaille

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  1. Jake Herb
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  2. Maria Curotto de Lafaille
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Correspondence to Jake Herb.

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Herb, J., Curotto de Lafaille, M. Pre-existing antibody allows for maturation of new B cells in ‘recall’ germinal centres. Nat Rev Immunol 24, 234 (2024). https://doi.org/10.1038/s41577-024-01012-w

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