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To whom B cells toll extrafollicular responses

Genes & Immunity volume 24, pages 285–286 (2023)Cite this article

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Prophylactic induction of humoral responses has proven to be the best option in preventing infection from highly virulent pathogens, but responses induced after immunization often take significant time to generate antigen-specific antibodies to a level of functional protection. This is due to the kinetics of the germinal center (GC) response, which requires participating B cells to undergo several rounds of proliferation and somatic hypermutation within the GC to finetune their B cell receptor (BCR) for enhanced antigen binding and eventual differentiation into antibody-secreting plasma cells (ASCs), a process that takes several days to mature and even longer to precipitate functional protection. However, there is evidence for the production of neutralizing antibodies early after infection and independent of GCs, which are generated by ASC forming clusters or “foci” in the extrafollicular compartment of secondary lymphoid tissues. Our recently published work, “Toll-like receptor mediated inflammation directs B cells towards protective antiviral extrafollicular responses” (EFR) provides experimental evidence that these rapid responses are protective and regulated by innate signals that trigger these “emergency responses” [1].

These data not only identify EFR as an untapped source of potentially protective antibodies, but also highlight the importance of the inflammatory milieu as a driver of EFR generation, expansion, and maintenance. Whether this innate signaling-mediated drive towards robust early plasma cell differentiation comes at the cost of maximally effective later-developing GCs remains an important open question.

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Fig. 1: TLR-mediated polarization of B cell fates.

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Authors and Affiliations

  1. David H. Koch Institute for Integrative Cancer Research, Massachussetts Institute of Technology, Boston, MA, USA

    Jonathan H. Lam

  2. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Lyme and Tickborne Diseases Research and Education Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Nicole Baumgarth

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  1. Jonathan H. Lam
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  2. Nicole Baumgarth
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JHL and NB both conceptualized and wrote the manuscript.

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Correspondence to Nicole Baumgarth.

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The authors declare no competing interests.

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Lam, J.H., Baumgarth, N. To whom B cells toll extrafollicular responses. Genes Immun 24, 285–286 (2023). https://doi.org/10.1038/s41435-023-00226-7

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