Deletion of IL-4Rα signaling on B cells limits hyperresponsiveness depending on antigen load
Division of Immunology and ICGEB researchers Dr Sabelo Hadebe, Dr Jermaine Khumalo, Dr Martyna Scibiorek, Ms Amkele Ngomti, Ms Nontobeko Mthembu, Ms Sandisiwe Mangali, Dr Hlumani Ndlovu, Dr Frank Kirstein and Professor Frank Brombacher, recently authored a paper in JACI. The paper published in December 2020 is entitled "Deletion of IL-4Rα signaling on B cells limits hyperresponsiveness depending on antigen load". The paper was highlighted in The Editors’ Choice, JACI.
The paper was highlighted in: The Editors' Choice, The Journal of Allergy and Clinical Immunology, Volume 148, Issue 1, July 01, 2021 - https://doi.org/10.1016/j.jaci.2021.05.022
Blocking IL-4Ra on B cells: More than IgE
The function of B cells in allergic asthma is contradictory which suggests a complex function of these cells in disease pathogenesis. Individuals with asthma have higher serum IgE to specific triggering allergens such as House Dust Mites (HDM) which perpetuates a cascade of pathological inflammation including activation of mast cells and basophils. Finding interventions that reduce pathological effects such as those initiated by HDM-specific IgE or the B cells that produce IgE could be of great benefit in limiting disease and improving quality of life. Hadebe et al., investigated how interleukin 4 receptor alpha (IL-4Ra) specifically in the B cells can be targeted for therapy using an HDM experimental model. Mice sufficient or deficient of IL-4Ra were challenged with both high dose and low dose HDM.
Key findings of the study included:
- Animals lacking the IL-4Ra on B cells, were unable to produce IgE.
- There was also a reduction in other disease parameters such airway hyperreactivity, a major cause of reduced airflow in asthmatics and also cytokines IL-4, IL-5 an IL-13 produced by CD4 T helper cells.
- B cells unresponsive to IL-4Ra were unable to produce IL-5 in the absence of IL-4Ra.
- Intriguing IL-4Ra responsiveness was prominently evident when HDM allergen was at low levels, in line with other studies that suggests a load dependent function of B cells.
- Mechanistically, the study suggested that blocking IL-4Ra on B cells reduced signals required for B cell and T cell contact in germinal centres, an area where long-lived memory B cells and plasma cells are produced (See GA figure).
This study doi: https://doi.org/10.1016/j.jaci.2020.12.635 highlighted a need to target IL-4Ra on B cells not only for IgE reduction, but for overall pathological effects, which could increase airflow and reduce granulocytic inflammation.
Article source - THE EDITORS’ CHOICE VOLUME 148, ISSUE 1, P53-58, JULY 01, 2021
View the paper - Deletion of IL-4Rα signaling on B cells limits hyperresponsiveness depending on antigen load
