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

Authors: HARDY, LAKEYA - University Of North Carolina; SMEEKENS, JOHANNA - University Of North Carolina; RAGHUWANSHI, DHARMENDRA - University Of Alberta; SARKAR, SUSMITA - University Of Alberta; DASHKAN, GOUR - University Of Alberta; Rogers, Stephen; Maleki, Soheila; BURKS, WESLEY - University Of North Carolina; PAULSON C, JAMES - Scripps Institute; MACAULEY, MATTHEW - University Of Alberta; KULIS, MICHAEL - Duke University School Of Medicine

Submitted to: Journal of Allergy Clinical Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/12/2022
Publication Date: 7/12/2022
Citation: Hardy, L.C., Smeekens, J., Raghuwanshi, D., Sarkar, S., Dashkan, G.C., Rogers, S.I., Maleki, S.J., Burks, W.A., Paulson C, J.C., Macauley, M.S., Kulis, M.D. 2022. Targeting CD22 on Memory B cells to induce tolerance to peanut allergens. Journal of Allergy Clinical Immunology. 150(6):1476-1485. https://doi.org/10.1016/j.jaci.2022.06.022.
DOI: https://doi.org/10.1016/j.jaci.2022.06.022

Interpretive Summary: Circulating immunoglobulin E (IgE) antibodies and subsequent severe allergic reactions to peanut are sustained and propagated by recall of peanut allergen-specific memory B cells. We aimed to determine whether targeting mouse and human CD22, a molecule on peanut-specific memory B cells induces tolerance to peanut allergens. Liposome spheres co-displaying peanut allergens (Ara h 1, 2, or 3) and CD22 ligand (CD22L)were constructed and injected into in various mouse models of peanut allergy. To investigate memory B cells, the splenocytes from peanut-sensitized mice were transferred into unsenstized animals. Reconstituted mice received the CD22L sphere displaying the allergens or an immunogenic liposome control, followed by a peanut allergen boost and, later, a challenge with individual peanut allergens. To assess the effects of the liposomes on human B cells, human immune cells were injected into specialized mice, followed by administration of human CD22L and later a whole peanut extract boost. Blood was collected to quantify WPE-, Ara h 1-, 2-, and 3-specific immunoglobulins. Mouse with CD22 and allergen displaying lyposomes significantly suppressed systemic memory to Ara h 1, 2 and 3 in two of the mouse models, as demonstrated by reduced allergen-specific immunoglobulin antibodies IgE, IgG1, and anaphylaxis upon challenge. Importantly, two doses of CD22L led to prolonged tolerance for at least three months. Human CD22L displayed similar suppression in mice expressing human CD22 on B cells. Finally, human B cells were tolerized in vivo in NSG mice by CD22L. In conclusion, antigen-specific exploitation of CD22 on memory B cells can induce systemic immune tolerance.

Technical Abstract: Circulating IgE and subsequent severe allergic reactions to peanut are sustained and propagated by recall of peanut allergen-specific memory B cells. We 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) co-displaying peanut allergens (Ara h 1, 2, or 3) and high-affinity CD22 ligand (CD22L-STALs) were employed in various mouse models (BALB/cJ, C57BL/6, human CD22 transgenic, 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 naïve 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-, Ara h 1-, 2-, and 3-specific immunoglobulins. Mouse CD22L-STALs (mCD22L-STALs) significantly suppressed systemic memory to Ara h 1, 2 and 3 in BALB/cJ and C57BL/6 mice, as demonstrated by reduced allergen-specific IgE, IgG1, and anaphylaxis upon challenge. Importantly, two doses of mCD22L-STALs led to prolonged tolerance for at least three 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.