IgE⁺ plasmablasts identified as “rapid-response unit” for seasonal allergy relapse

For millions of allergy sufferers worldwide, specific seasons predict periodic symptoms relapse. The immunological hallmark of this phenomenon is a sharp, transient spike in blood levels of immunoglobulin E (IgE) antibodies against allergens like pollen. While this pattern is well-known, the precise cellular source driving this rapid, potent "secondary response" and its pathological consequences have remained elusive. Conventional theory speculated that it might involve the reactivation of memory B cells, but direct evidence was lacking.

On this premise, a rigorous longitudinal study was conducted by researchers from Russia and Austria, led by Professor Rudolf Valenta, and published in Volume 2, Issue 2 of the journal Immunity & Inflammation on January 13, 2026. They tracked the immune dynamics of multiple birch pollen-allergic patients throughout an entire pollen season cycle. The research found that during pollen exposure, patients' levels of IgE antibodies against the major allergen Bet v 1 increased significantly, while levels of IgG antibodies against the same protein did not increase synchronously. This indicated that seasonal allergy relapse mobilizes a distinct response pathway independent of conventional humoral immune memory.

By using a therapeutic anti-IgE antibody (omalizumab) as a specific probe, the researchers successfully "locked onto" a rare population of B cells carrying membrane-bound IgE in the patients' peripheral blood. Deep phenotypic analysis revealed that these cells were not classic memory B cells but rather plasmablasts with a CD27⁺CD38⁺CD20^low signature. Their numbers expanded significantly during the pollen season, directly serving as the source of the secondary IgE antibody production.

A crucial finding of the study was elucidating the direct pathological function of these IgE⁺ plasmablasts. The team observed that in the absence of allergen exposure, the sensitivity of patients' effector cells (e.g., basophils) to allergens declined. However, when the pollen season arrived, the newly generated IgE antibodies from plasmablasts acted like a "special delivery," rapidly reloading the high-affinity IgE receptors (FcεRI) on the surface of effector cells. This restored and potentially amplified cellular reactivity, directly triggering the relapse of clinical symptoms—a process the authors term "reloading the effector cells."

The study further analyzed the genetic characteristics of the IgE antibodies produced by these plasmablasts using molecular techniques. The results showed striking similarities (clonally related) in the IgE antibody genes targeting Bet v 1, even across different patients, and sequences ranged from highly mutated to nearly unmutated. This suggests that during initial allergic sensitization, the immune system selects and fixes a set of specialized B cell clones. These act as a "rapid-response reserve," quickly mobilized and differentiated into IgE⁺ plasmablasts upon re-encounter with the allergen.

"This research changes our understanding of allergic immune memory," explained the study's corresponding author, Professor Valenta. "We have confirmed that it is not memory B cells, but the specialized IgE-secreting plasmablasts, that act as the 'ignition switch' for acute seasonal allergy attacks. This explains why the allergic reaction is so swift and highly specific."

This discovery holds significant translational potential. Because plasmablasts are short-lived, highly active cells, they represent a more suitable target for short-term intervention compared to long-lived plasma cells or quiescent memory B cells. In theory, specifically eliminating or inhibiting these IgE⁺ plasmablasts just before or during the allergy season could prevent or mitigate symptom onset without affecting the long-term function of the overall immune system. This provides a novel scientific rationale for developing precise, "on-demand" or seasonal allergy treatment strategies.

Furthermore, monitoring the number of allergen-specific IgE⁺ plasmablasts in peripheral blood may, in the future, serve as a novel biomarker for predicting disease activity or assessing treatment efficacy.

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Reference
DOI: 10.1007/s44466-025-00018-w

About Immunity & Inflammation
Immunity & Inflammation is a newly launched open-access journal co-published by the Chinese Society for Immunology and Springer Nature under the leadership of Editors-in-Chief Prof. Xuetao Cao and Prof. Jules A. Hoffmann. Immunity & Inflammation aims to publish research on major scientific questions and cutting-edge advances that explore groundbreaking discoveries and insights across the spectrum of immunity and inflammation, from basic science to translational and clinical research.

Website: https://link.springer.com/journal/44466

About Authors

Prof. Rudolf Valenta from the Medical University of Vienna, Austria
Rudolf Valenta is a Professor at the Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna. He is a member of the Austrian Academy of Sciences. His research focuses on allergen diagnosis, vaccine development, immunotherapy for allergy.

Funding information
This work was supported by Megagrant of the Government of the Russian Federation [075–15–2021–632 (14.W03.31.0024)], DANUBE ARC research program of the Country of Lower Austria, the Austrian Science Fund (FWF, project P34472-B), and the Russian Science Foundation (Project 23–15-00432).