Targeting CD22 on memory B cells to induce tolerance to peanut allergens

• Published in: Journal of allergy and clinical immunology 2022-12, Vol.150 (6), p.1476-1485.e4
• Main Authors: Hardy, LaKeya C., Smeekens, Johanna M., Raghuwanshi, Dharmendra, Sarkar, Susmita, Daskhan, Gour C., Rogers, Stephen, Nycholat, Corwin, Maleki, Soheila, Burks, A. Wesley, Paulson, James C., Macauley, Matthew S., Kulis, Michael D.
• Format: Article
• Language: English
• Subjects: adoptive transfer; Allergens; anaphylaxis; Animals; Arachis; B cell; CD22; food allergy; humanized mouse model; Humans; Immune Tolerance; Memory B Cells; Mice; Mice, Inbred C57BL; peanut allergens; Peanut sensitization; Sialic Acid Binding Ig-like Lectin 2; siglecs; tolerance
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2022.06.022

Circulating IgE and subsequent severe allergic reactions to peanut are sustained and propagated by recall of peanut allergen-specific memory B cells. This study aimed to determine whether targeting mouse and human CD22 on peanut-specific memory B cells induces tolerance to peanut allergens. Siglec-engaging tolerance-inducing antigenic liposomes (STALs) codisplaying peanut allergens (Ara h 1, Ara h 2, or Ara h 3) and high-affinity CD22 ligand (CD22L-STALs) were employed in various mouse models (BALB/cJ, C57BL/6, human CD22 transgenic, and NSG) of peanut allergy. To investigate memory B cells, a conferred memory model was used in which splenocytes from peanut-sensitized mice were transferred into naive animals. Reconstituted mice received either CD22L-STALs or an immunogenic liposome control, followed by a peanut allergen boost and later a challenge with individual peanut allergens. To assess the effects of CD22L-STALs on human B cells, PBMCs were injected into NSG mice, followed by administration of human CD22L-STALs (hCD22L-STALs) and later a whole peanut extract boost. Blood was collected to quantify WPE- and Ara h 1–, 2–, and 3–specific immunoglobulins. Mouse CD22L-STALs (mCD22L-STALs) significantly suppressed systemic memory to Ara h 1, Ara h 2, and Ara h 3 in BALB/cJ and C57BL/6 mice, as demonstrated by reduced allergen-specific IgE, IgG1, and anaphylaxis on challenge. Importantly, 2 doses of mCD22L-STALs led to prolonged tolerance for at least 3 months. hCD22L-STALs displayed similar suppression in mice expressing human CD22 on B cells. Finally, human B cells were tolerized in vivo in NSG mice by hCD22L-STALs. Antigen-specific exploitation of CD22 on memory B cells can induce systemic immune tolerance.