Rudolf Valenta, of the Medical University of Vienna

Rudolf Valenta

Seasonal Allergen Exposure Recalls IgE Plasmablasts in Birch Allergy, With Rudolf Valenta

A new longitudinal study found that IgE⁺ plasmablasts are the primary cellular drivers of seasonal IgE increases in birch pollen allergy.

, of the Medical University of Vienna, about the study’s implications. He highlighted the significance of increased seasonal IgE without a corresponding IgG response.

“Look, this is a very hot debate,” Valenta said. “There [are], I would say, two different schools here. There's one school that comes from mouse immunology. In the mouse, there is something like a sequential car switch, so if you start to sensitize a mouse to develop IgG antibodies, it's usually done by injection or by high doses of inhalation, the mouse develops IG and IgG antibodies against the same epitopes. In the human, this is not the case, because if the human would produce the IgG antibodies against the same epitopes as IgE, the person would be protected and not be allergic. The story is that [people] …push this idea of the sequential car switch in, I dare to say, very important journals here, and it's true for the mouse. The thing is, [when we] undertake our investigations in patients and in the patient, it's different.”

In this study, patients have no induction of IgG antibodies, nor are these antibodies against the IgG epitopes. However, this is the case of IgE antibodies.

If seasonal exposure triggered IgG against the same epitopes, it would act like natural immunotherapy, generating blocking IgG antibodies. Except, this does not happen; people become more sensitized after the season.

“So that's one of the reasons why we put a little bit of emphasis on this,” Valenta continued. “It’s a major observation.”

Bet v 1–specific IgE levels increased significantly during peak pollen season compared with pre-season (TP1 vs TP3; 

 < .01) and declined after the season ended (TP3 vs TP5;

 < .05). In contrast, bet v 1–specific IgG1 and IgG4 levels did not show significant seasonal changes.

Flow cytometry demonstrated a significant rise in circulating IgE⁺ plasmablasts (CD19⁺CD27⁺CD38⁺CD20low) during pollen exposure. Epitope mapping showed that the seasonal IgE boost targeted pre-existing conformational epitopes of Bet v 1, rather than generating new specificities. Functionally, this plasmablast-derived IgE reloaded effector cells, restoring allergen-specific basophil activation that had waned outside the season.

Valenta said that omalizumab could have upstream effects beyond neutralizing circulating IgE. Because the antibody does not bind IgE already attached to high- or low-affinity receptors, it may selectively target IgE-expressing B-lineage cells. This raises the possibility of weakening IgE memory responses, although clinical studies are needed.

“What we actually proposing is that this antibody could be used to eliminate such cells, and that could be a very strong bullet in killing IG responses in patients,” Valenta said. “It's different from the idea of the Regeneron [company], who want to prevent the gas switch, because this is something we think is not so important [for] the patients. We also say it's not the plasma cells, because they have a kind of continuous production that fades away, so we have in the middle what we think is a crucial cell that we can target.”

Byazrova, M., Litovkina, A., Eckl-Dorna, J. 

 Seasonal allergen exposure recalls IgE+ plasmablasts to reload allergic effector cells. 

https://doi.org/10.1007/s44466-025-00018-w

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Valenta discusses how seasonal allergen exposure selectively boosts IgE production through plasmablast recall, without a coordinated IgG response.


Rudolf Valenta

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