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

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.