Omalizumab may decrease IgE synthesis by targeting membrane IgE+ human B cells.
Omalizumab may decrease IgE synthesis by targeting membrane IgE+ human B cells.
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DOI：
10.1186/2045-7022-3-29
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发表时间：
2013-09-02
影响因子：
4.4
通讯作者：
Rosenwasser LJ
中科院分区：
文献类型：
--
作者：
Chan MA;Gigliotti NM;Dotson AL;Rosenwasser LJ
奥马珠单抗是一种人源化抗IgE单克隆抗体，用于治疗过敏性哮喘。治疗导致血清IgE水平降低、嗜酸性粒细胞和B细胞计数降低。体外研究和动物模型支持奥马珠单抗抑制B细胞IgE合成并通过诱导细胞凋亡或诱导无反应性或耐受性消除IgE表达细胞的假设。我们研究了奥马珠单抗对人扁桃体B细胞存活和IgE合成相关基因的影响。扁桃体B细胞用IL-4加抗-CD 40抗体刺激，以在存在或不存在奥马珠单抗的情况下诱导类转换重组以产生IgE。评估细胞活力并提取RNA以检查参与IgE合成的特异性基因。我们发现奥马珠单抗减少了活细胞数量，但这不是通过诱导细胞凋亡。奥马珠单抗处理的B细胞中IL-4 R和生殖系C β mRNA水平以及膜IgE+细胞的数量降低。这些数据表明，奥马珠单抗可能通过特异性靶向携带IgE的膜B细胞并诱导无反应性状态，降低人B细胞的IgE合成。
Omalizumab, is a humanized anti-IgE monoclonal antibody used to treat allergic asthma. Decreased serum IgE levels, lower eosinophil and B cell counts have been noted as a result of treatment. In vitro studies and animal models support the hypothesis that omalizumab inhibits IgE synthesis by B cells and causes elimination of IgE-expressing cells either by induction of apoptosis or induction of anergy or tolerance. We examined the influence of omalizumab on human tonsillar B cell survival and on the genes involved in IgE synthesis. Tonsillar B cells were stimulated with IL-4 plus anti-CD40 antibody to induce class switch recombination to IgE production in the presence or absence of omalizumab. Cell viability was assessed and RNA extracted to examine specific genes involved in IgE synthesis. We found that omalizumab reduced viable cell numbers but this was not through induction of apoptosis. IL-4R and germline Cϵ mRNA levels were decreased as well as the number of membrane IgE+ cells in B cells treated with omalizumab. These data suggest that omalizumab may decrease IgE synthesis by human B cells by specifically targeting membrane IgE-bearing B cells and inducing a state of anergy.