Oral Presentation Australasian Cytometry Society 41st Annual Conference

New developments in immunophenotyping of human B-cells: IgE, IgG subclasses and tetramers (24273)

Menno C van Zelm 1
  1. Immunology and Pathology, Monash University, Melbourne, VIC, Australia

Allergies are an increasingly common group of chronic diseases that affect over 20% of all Australians. The clinical picture varies depending on sensitisation to the specific protein (allergen) and ranges from lung constriction (asthma), rhinitis (hay fever), intestinal problems (food allergies) to anaphylaxis (venom allergies and food allergies). These acute and chronic responses can cause high morbidity, negatively impacting daily life and can be life-threatening, thus forming a major global health problem.

The key mediator of the disease is immunoglobulin E (IgE), which is a type of antibody produced by B cells, and which triggers the release of allergic mediators upon allergen binding. Several forms of allergy, including to bee venom, can be treated by immunotherapy which involves exposing an allergic individual to increasing doses of allergen. Typically, desensitisation following immunotherapy is associated with increased serum IgG4 without affecting IgE.

Despite all insights into the allergic response, the B cells that produce IgE and IgG4 are rather enigmatic. This is mostly due to their scarcity.

In previous and ongoing work in my group, we have developed flowcytometry tools and panels to reliably detect IgE and IgG-subclass expressing B cells. These have generated new insights into their origin and maturation pathways in health and disease. In my presentation, I will highlight these developments, as well as ongoing work using recombinant allergen tetramers to detect and isolate allergen-specific B cells from patients before and after immunotherapy.

These new developments will enable us to examine the culprits of disease, as well as the cells associated with successful immunotherapy. Hence, this could drive single-cell immune monitoring of treatment, as well as the identification of new targets for treatment.

  1. M.A. Berkowska, J.J. Heeringa, E. Hajdarbegovic, M. van der Burg, H.B. Thio, P.M. van Hagen, L. Boon, A. Orfao, J.J.M. van Dongen, M.C. van Zelm (2014) Human IgE+ B cells are derived from T cell–dependent and T cell–independent pathways. J Allergy Clin Immunol. 134(3):688-697.e6.
  2. J.J. Heeringa, A.F. Karim, J.A.M. van Laar, R.M. Verdijk, D. Paridaens, P.M. van Hagen, M.C. van Zelm (2017) Expansion of blood IgG4+ B-cells, Th2 and regulatory T cells in IgG4-related disease. J Allergy Clin Immunol. 141(5):1831-1843.e10.
  3. J.J. Heeringa, L. Rijvers, N.J. Arends, G.J. Driessen, S.G. Pasmans, J.J.M. van Dongen, J.C. de Jongste, M.C. van Zelm (2018) IgE-expressing memory B cells and plasmablasts are increased in blood of children with asthma, food allergy and atopic dermatitis. Allergy doi: 10.1111/all.13421.
  4. B.G. de Jong, H. IJspeert, L. Marques, M. van der Burg, J.J.M. van Dongen, B.G. Loos, M.C. van Zelm. (2017) Human IgG2- and IgG4-expressing memory B cells display enhanced molecular and phenotypic signs of maturity and accumulate with age. Immunol Cell Biol. 95(9):744-752.