B cells establish, but do not maintain, long‐lived murine anti‐peanut IgE^a

Abstract

Background Peanut allergy has been reported to be transferred to tolerant recipients through organ and bone marrow 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 peanut allergy 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 peanut allergy. We also treated peanut-allergic mice with anti-CD20 antibody and measured IgE levels throughout treatment. Results Purified B220+ cells from peanut-allergic splenocytes and purified CD4+ cells from naïve splenocytes are the minimal requirements for the adoptive transfer of peanut allergy. 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 in the bone marrow. Adoptive transfer of bone marrow and spleen cells from allergic donors treated with anti-CD20 antibody does not result in the transfer of peanut allergy in naïve recipients, demonstrating that anti-CD20 antibody treatment depletes B cells capable of differentiating into peanut-specific IgE antibody secreting cells. Conclusions and Clinical Relevance Peanut allergy can be established in a naïve hosts with B220+ cells from peanut-allergic donors and CD4+ cells from peanut-naïve 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 peanut allergy and provide evidence that long-lived anti-peanut IgE levels may be maintained by long-lived antibody secreting cells.

Prolonged Treatment of Peanut-Allergic Mice with Bortezomib Significantly Reduces Serum Anti-Peanut IgE but Does Not Affect Allergic Symptoms

“…In a previous study, treatment of Pn-allergic mice with anti-CD20 antibody led to prolonged depletion of CD19 + cells in the peripheral blood, peritoneum, and SPL, as well as depletion of mature, but not immature, CD19 + cells in the BM; however, anti-Pn IgE and symptoms were not affected [14]. These results suggest that long-lived PCs, rather than CD20 + cells, may be central to maintaining long-lived IgE.…”

“…Female, C3H/HeJ mice, were acquired, housed, fed, sensitized, challenged, and scored as described [14]. Sensitization occurred from weeks -8 to -5, and the first challenge occurred at week -3.…”

“…Cells from the BM and SPL were stained as previously described [14]. Anti-Pn IgG, total IgG, and total IgE ASCs were enumerated with ELISPOT [14], and serum anti-Pn IgE and IgG1 antibodies were detected as previously described [14,16].…”

“…In a previous study, we have shown that CD20 + B cells do not maintain long-lived murine anti-Pn IgE [14]. Therefore, we hypothesized that anti-Pn IgE was maintained by ASCs.…”

“…The C3H/HeJ murine model of Pn allergy generates high serum anti-Pn IgE that is long-lived, persisting for at least 21 weeks after challenge [14]. In a previous study, we have shown that CD20 + B cells do not maintain long-lived murine anti-Pn IgE [14].…”