Photo Credit: Ulrike Leone

The following is a summary of “Subcutaneous immunotherapy for bee venom allergy induces epitope spreading and immunophenotypic changes in allergen-specific memory B cells,” published in the August 2024 issue of Allergy and Immunology by McKenzie et al.

Allergen immunotherapy (AIT) is currently recognized as the sole disease-modifying intervention for allergic disorders. Recent research has revealed phenotypic alterations in  memory B cells (Bmem) after four months of sublingual AIT for ryegrass pollen allergy. However, it remains unclear whether similar modifications occur with subcutaneous allergen immunotherapy (SCIT) and how these changes impact the epitope specificity of Bmem. This study aimed to investigate the phenotypic characteristics and antigen receptor sequences of Bmem specific to Api m 1, the principal bee venom (BV) allergen, both before and after ultra-rush SCIT for BV allergy. Using recombinant Api m 1 tetramers, basophil activation was assessed in a cohort of BV-allergic individuals prior to and following SCIT. Advanced flow cytometry was employed to evaluate and isolate Api m 1-specific Bmem, followed by the sequencing and structural modeling of immunoglobulin genes from individual Api m 1-specific Bmem onto the Api m 1 allergen. 

Results demonstrated that SCIT induced class switching of Api m 1-specific Bmem towards IgG2 and IgG4 subclasses, along with upregulated expression of the surface markers CD23 and CD29. This phenotypic shift highlights a regulatory Bmem profile, which may contribute to the immunomodulatory effects observed with SCIT. Moreover, structural modeling of the immunoglobulin from these Bmem identified a new and diverse repertoire of Api m 1 allergen epitopes, suggesting that SCIT not only modifies the antibody response but may also influence epitope recognition. Importantly, the study revealed epitopes that appear to be preferentially targeted by immunoglobulins post-SCIT, indicating potential mechanistic pathways through which SCIT drives allergen tolerance. 

These findings provide new insights into how AIT influences epitope specificity and the functional characteristics of allergen-specific Bmem, underscoring the therapeutic potential of SCIT in reshaping the immune response to allergens and advancing precision medicine approaches in allergy treatment.

Source: sciencedirect.com/science/article/pii/S0091674924009023