Moutsoglou D M, Dreskin S C
Division of Allergy and Clinical Immunology, Departments of Medicine and Immunology, University of Colorado Denver, Aurora, CO, USA.
Clin Exp Allergy. 2016 Apr;46(4):640-53. doi: 10.1111/cea.12715.
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.
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.
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.
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.
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.
据报道,花生过敏(PNA)可通过器官和骨髓(BM)移植转移至耐受受体。T细胞和B细胞在建立花生过敏中的作用,以及B细胞亚群在维持终身抗花生IgE水平中的作用尚不清楚。
确定小鼠PNA转移的细胞需求,并确定CD20(+)细胞在维持长期抗花生IgE水平中的作用。
我们开发了一种新型的过继转移模型来研究小鼠PNA转移的细胞需求。我们还用抗CD20抗体处理花生过敏(PA)小鼠,并在整个治疗过程中测量IgE水平。
来自PA脾细胞的纯化B220(+)细胞和来自未致敏(NA)脾细胞的纯化CD4(+)细胞是PNA过继转移的最低要求。用抗CD20抗体长期治疗过敏小鼠会导致B细胞亚群显著减少,但不影响抗花生IgE水平、症状或BM中IgE抗体分泌细胞(ASC)的数量。用抗CD20抗体处理的过敏供体的BM和脾细胞过继转移不会导致NA受体中PNA的转移,表明抗CD20抗体处理会耗尽能够分化为花生特异性IgE ASC的B细胞。
花生过敏可在NA宿主中通过PA供体的B220(+)细胞和花生-NA供体的CD4(+)细胞建立。然而,用抗CD20抗体长期消耗B220(+)细胞并不影响抗花生IgE水平。这些结果突出了B细胞在PNA发展中的新作用,并提供了证据表明长期抗花生IgE水平可能由长寿ASC维持。