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

Authors

Mohammed, S., Sbihi, Z., Laignel, P., Houtia, I., Haddou, S., Procopio, E., Morales, O., Franck, G., Caligiuri, G., Nicoletti, A., Le Borgne, M.

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.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 14 Oct 2026.

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