Background Peanut allergy (PNA) has been reported to be transferred to tolerant recipients through organ and bone marrow (BM) transplantation. The roles T and B cells play in establishing, and the roles B cell subsets play in maintaining lifelong anti-peanut IgE levels are unknown. Objectives: To determine the cellular requirements for the transfer of murine PNA and to determine the role CD20+ cells play in maintaining long-lived anti-peanut IgE levels. Methods: We developed a novel adoptive transfer model to investigate the cellular requirements for transferring murine PNA. We also treated peanut-allergic (PA) mice with anti-CD20 antibody and measured IgE levels throughout treatment. Results: Purified B220+ cells from PA splenocytes and purified CD4+ cells from naïve (NA) splenocytes are the minimal requirements for the adoptive transfer of PNA. Prolonged treatment of allergic mice with anti-CD20 antibody results in significant depletion of B cell subsets but does not affect anti-peanut IgE levels, symptoms, or numbers of IgE antibody secreting cells (ASCs) in the BM. Adoptive transfer of BM and spleen cells from allergic donors treated with anti-CD20 antibody does not result in the transfer of PNA in NA recipients, demonstrating that anti-CD20 antibody treatment depletes B cells capable of differentiating into peanut-specific IgE ASCs. Conclusions and Clinical Relevance: Peanut allergy can be established in a NA hosts with B220+ cells from PA donors and CD4+ cells from peanut-NA donors. However, long-term depletion of B220+ cells with anti-CD20 antibody does not affect anti-peanut IgE levels. These results highlight a novel role for B cells in the development of PNA and provide evidence that long-lived anti-peanut IgE levels may be maintained by long-lived ASCs.
Bibliographical noteFunding Information:
We thank Genentech Inc. for kindly proving the anti- CD20 and IC Abs for these experiments. We also thank Drs. John C. Cambier, Philippa Marrack, Andrew Fontenot, Angie Ribera, and Rafeul Alam for suggestions on analysis and experimentation. We thank Dr. Raul Torres for critical review of the manuscript, and we thank Qian Wang and Dr. Yonghua Zhuang for preparation of Ara h 2 and Ara h 6 proteins devoid of PN lectins. Sources of support: R01-AI099029 from the National Institute of Allergy and Infectious Diseases (to S.C. Dreskin), a mini-grant from the American Academy of Allergy, Asthma, and Immunology (AAAAI) (to S.C. Dreskin), a pre-doctoral grant from the Colorado Clinical & Translational Science s Institute (NIH/NCATS Colorado CTSI Grant Number TL1 TR000155) (to D. Moutsoglou), and by University of Colorado Division of Allergy and Clinical Immunology divisional funds.
- Adoptive transfer
- Antibody secreting cell
- Memory B cell