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PreprintCC BY-NCbioRxiv

Fever-range temperature enhances B cells in vitro but is dispensable for the germinal center in vivo

  1. 1Université Paris Cité and Université Sorbonne Paris Nord, INSERM, LVTS, F-75018 Paris, France

Abstract

Fever is a conserved physiological response to immune activation characterized by elevated body temperature. While hyperthermia enhances innate and T cell immunity, its role in shaping the B cell compartment remains poorly defined, despite B cells' role in long-term protection. Understanding how temperature modulates B cell physiology is relevant to vaccine strategies, particularly fever management around immunization. Therefore, we investigated the influence of fever-range thermal changes on humoral immunity. To decipher the direct effects, primary B cells from C57BL/6 mice were stimulated in vitro under mild hyperthermic conditions (~1.5{degrees}C increase). Fever-range temperature enhanced B cell activation, facilitated entry into cell division, and increased antigen presentation to CD4+ T cells, while transcriptomic analysis revealed enrichment of pathways involved in protein synthesis and mitochondrial respiration. To determine whether these intrinsic effects translated into altered humoral immunity in vivo, we developed a novel tunable implant-based system to induce localized, 48-hour hyperthermia around a draining lymph node in awake mice without altering core body temperature. Following subcutaneous NP-OVA/alum immunization, localized hyperthermia localized hyperthermia did not enhance antigen-specific germinal center B cell expansion, antibody titers or IgG affinity on day 9. Moreover, heating during priming did not affect the recall humoral response after a booster on day 21. Thus, fever-range temperature directly modulates murine B cell function in vitro but does not enhance humoral immunity in vivo, indicating that the biological consequences of intrinsic B cell thermosensitivity depend on its integration within the multicellular and inflammatory signals shaping germinal center responses.

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BibTeX
@misc{mohammed2026feverrange,
  title = {{Fever-range temperature enhances B cells in vitro but is dispensable for the germinal center in vivo}},
  author = {S. Mohammed and Z. Sbihi and P. Laignel and I. Houtia and S. Haddou and E. Procopio and O. Morales and G. Franck and G. Caligiuri and A. Nicoletti and M. Le Borgne},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.12.757555},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.12.757555v1},
  note = {CC BY-NC},
}
RIS
TY  - UNPB
TI  - Fever-range temperature enhances B cells in vitro but is dispensable for the germinal center in vivo
AU  - S. Mohammed
AU  - Z. Sbihi
AU  - P. Laignel
AU  - I. Houtia
AU  - S. Haddou
AU  - E. Procopio
AU  - O. Morales
AU  - G. Franck
AU  - G. Caligiuri
AU  - A. Nicoletti
AU  - M. Le Borgne
PY  - 2026
DA  - 2026/10/12
PB  - bioRxiv
DO  - 10.64898/2026.10.12.757555
UR  - https://www.biorxiv.org/content/10.64898/2026.10.12.757555v1
AB  - Fever is a conserved physiological response to immune activation characterized by elevated body temperature. While hyperthermia enhances innate and T cell immunity, its role in shaping the B cell compartment remains poorly defined, despite B cells' role in long-term protection. Understanding how temperature modulates B cell physiology is relevant to vaccine strategies, particularly fever management around immunization. Therefore, we investigated the influence of fever-range thermal changes on humoral immunity. To decipher the direct effects, primary B cells from C57BL/6 mice were stimulated in vitro under mild hyperthermic conditions (~1.5{degrees}C increase). Fever-range temperature enhanced B cell activation, facilitated entry into cell division, and increased antigen presentation to CD4+ T cells, while transcriptomic analysis revealed enrichment of pathways involved in protein synthesis and mitochondrial respiration. To determine whether these intrinsic effects translated into altered humoral immunity in vivo, we developed a novel tunable implant-based system to induce localized, 48-hour hyperthermia around a draining lymph node in awake mice without altering core body temperature. Following subcutaneous NP-OVA/alum immunization, localized hyperthermia localized hyperthermia did not enhance antigen-specific germinal center B cell expansion, antibody titers or IgG affinity on day 9. Moreover, heating during priming did not affect the recall humoral response after a booster on day 21. Thus, fever-range temperature directly modulates murine B cell function in vitro but does not enhance humoral immunity in vivo, indicating that the biological consequences of intrinsic B cell thermosensitivity depend on its integration within the multicellular and inflammatory signals shaping germinal center responses.
ER  -