Reynolds Laboratory, Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
Front Immunol. 2020 Oct 15;11:557960. doi: 10.3389/fimmu.2020.557960. eCollection 2020.
Conflicting data has emerged regarding a role for eosinophils in IgA production, with some reports that eosinophils support both secretory and circulating IgA levels during homeostasis. Previous studies have compared antibody levels between wildtype and eosinophil-deficient mice, but these mice were obtained from different commercial vendors and/or were not littermates. Thus, the possibility remains that extrinsic environmental factors, rather than an intrinsic lack of eosinophils, are responsible for the reports of reduced IgA in eosinophil-deficient mice. Here we used wild-type and eosinophil-deficient (ΔdblGATA) mice that were purchased from a single vendor, subsequently bred in-house and either co-housed as adults, co-reared from birth or raised as littermates. We found no differences in the levels of secretory IgA or in the numbers of small intestinal IgA-producing plasma cells between wild-type and ΔdblGATA mice, demonstrating that under controlled steady-state conditions eosinophils are not essential for the maintenance of secretory IgA in the intestinal tract. While we found that levels of IgM and IgE were significantly elevated in the serum of ΔdblGATA mice compared to co-reared or co-housed wild-type mice, no significant differences in these or other circulating antibody isotypes were identified between genotypes in littermate-controlled experiments. Our results demonstrate that eosinophils are not required to maintain secretory or circulating IgA production and the absence of eosinophils does not impact circulating IgG1, IgG2b, IgM, or IgE levels during homeostasis. These findings emphasize the importance of optimally controlling rearing and housing conditions throughout life between mice of different genotypes.
关于嗜酸性粒细胞在 IgA 产生中的作用，出现了相互矛盾的数据，一些报告表明，在稳态期间，嗜酸性粒细胞支持分泌型和循环 IgA 水平。以前的研究比较了野生型和嗜酸性粒细胞缺陷型小鼠之间的抗体水平，但这些小鼠来自不同的商业供应商，或者不是同窝出生的。因此，仍然存在一种可能性，即外在环境因素而不是嗜酸性粒细胞的内在缺乏，导致了嗜酸性粒细胞缺陷型小鼠中 IgA 减少的报告。在这里，我们使用了从单一供应商购买的野生型和嗜酸性粒细胞缺陷型（ΔdblGATA）小鼠，随后在内部繁殖，并在成年时共同饲养、从出生起共同饲养或作为同窝饲养。我们没有发现野生型和 ΔdblGATA 小鼠之间分泌型 IgA 水平或小肠 IgA 产生浆细胞数量存在差异，这表明在受控的稳态条件下，嗜酸性粒细胞对于维持肠道中的分泌型 IgA 不是必需的。虽然我们发现与共同饲养或共同饲养的野生型小鼠相比，ΔdblGATA 小鼠的血清中 IgM 和 IgE 水平显著升高，但在同窝控制实验中，在这些或其他循环抗体同种型之间没有发现基因型之间的显著差异。我们的结果表明，嗜酸性粒细胞不需要维持分泌型或循环型 IgA 的产生，并且在稳态期间，嗜酸性粒细胞的缺失不会影响循环 IgG1、IgG2b、IgM 或 IgE 水平。这些发现强调了在不同基因型的小鼠之间，终生最佳控制饲养和饲养条件的重要性。
