Induction of IgG2 and IgG4 B‐cell memory following sublingual immunotherapy for ryegrass pollen allergy

• Published in: Allergy (Copenhagen) Vol. 75; no. 5; pp. 1121 - 1132
• Main Authors: Heeringa, Jorn J., McKenzie, Craig I., Varese, Nirupama, Hew, Mark, Bakx, Amy T. C. M., Aui, Pei M., Rolland, Jennifer M., O’Hehir, Robyn E., Zelm, Menno C.
• Format: Journal Article
• Language: English
• Published: Zurich Blackwell Publishing Ltd 01.05.2020; John Wiley and Sons Inc
• Subjects: Allergens; Allergic diseases; Allergies; Atopy; B cells; Flow cytometry; IgE; Immunoglobulin E; Immunoglobulin G; Immunological memory; Immunological tolerance; Immunomodulation; Immunomodulators; Immunoregulation; Immunotherapy; immunotherapy and tolerance induction; Leukocytes (mononuclear); Lymphocytes B; Lymphocytes T; Memory cells; Oral administration; Original; ORIGINAL ARTICLES; Peripheral blood mononuclear cells; Pollen; Rhinitis; Rhinoconjunctivitis
• ISSN: 0105-4538; 1398-9995; 1398-9995
• DOI: 10.1111/all.14073

Background While treatment for atopic rhinitis is aimed mostly to relieve symptoms, only allergen‐specific immunotherapy (AIT) is targeted to modify the natural history of allergic diseases. This results in sustained clinical tolerance, even when treatment has stopped. The immunomodulatory effects of AIT are attributed mainly to increased regulatory T‐cell function and increased allergen‐specific IgG4, yet little is known about the effect on the memory B‐cell compartment. Objective We aimed to examine the effects of AIT on the IgE‐ and IgG subclass‐expressing memory B cells. Methods We recruited 29 patients with atopic seasonal rhinoconjunctivitis and performed a longitudinal analysis of the peripheral immune compartment before, during, and after sublingual immunotherapy (SLIT) for allergy to temperate grass pollen, predominantly to ryegrass pollen (RGP; Lolium perenne). Using flow cytometry on peripheral blood mononuclear cells and serum immunoassays, we analyzed the effects of a 4 months preseasonal treatment regimen comprising two or three courses in consecutive years on circulating IgE+ and IgG+ memory B cells and allergen‐specific Ig levels. Results SLIT increased RGP‐specific serum IgG2 and IgG4, as well as the frequencies of IgG2+ and IgG4+ memory B cells, whereas no effect was observed on the IgE+ memory B‐cell compartment. Furthermore, SLIT enhanced proportions of regulatory T cells specific to RGP. These changes were associated with clinical improvement. Conclusion Our data provide evidence for immunological effects of SLIT on B‐cell memory. Skewing responses toward IgG2 and IgG4 subclasses might be a mechanism to suppress IgE‐mediated allergic responses. This study examines the effect of ryegrass pollen AIT on B‐cell responses in a population of 29 patients with allergic rhinitis. Successful immunotherapy for ryegrass pollen allergy increases allergen‐specific IgG2 and IgG4 serum levels, and proportions of IgG2‐ and IgG4‐expressing memory B cells. Skewing toward the anti‐inflammatory IgG2 and IgG4 subclasses might be a mechanism to suppress IgE‐mediated allergic responses.