Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras, Portugal.
Blood. 2013 Jul 11;122(2):209-18. doi: 10.1182/blood-2012-08-447136. Epub 2013 May 30.
B-cell numbers and immunoglobulin (Ig) titers can increase several logs during immune responses. In contrast to this plasticity and despite constant renewal, B-cell numbers are stable in the absence of immunization. We assessed the role of serum Igs in maintaining specific B-cell subset homeostasis at steady state. Using mice genetically deficient in secreted IgM only (secretory μ chain-deficient), in switched Igs and hypermutated IgM (activation-induced cytidine deaminase-deficient), or fully agammaglobulemic (AID(-/-)µS(-/-)), we dissected the contribution of different Ig classes to 4 phenotypes associated with loss of serum Igs: 1) increased splenic B-cell numbers, mostly of the B1 and marginal zone (MZ) B-cell subtypes; 2) enlarged germinal centers (GCs) in spleen and mesenteric lymph nodes; 3) enrichment in IRF4(+)CD138(-) plasmablast-like cells; and 4) overexpression of IgM in several cell subsets. Complementation experiments based on either mixed bone marrow reconstitution of chimeras or Ig infusion, and analysis of mice raised in germ-free conditions reveal a negative feedback mechanism in which MZ and B1 cell numbers are under the control of naturally secreted Igs as the result of an intrinsic property of the immune system, whereas GC development is under indirect control of secreted Igs that limit bacterial species triggering GC reactions.
B 细胞数量和免疫球蛋白 (Ig) 滴度在免疫反应期间可以增加几个对数。与这种可塑性形成对比的是，尽管不断更新，但在没有免疫接种的情况下，B 细胞数量是稳定的。我们评估了血清 Ig 在维持稳态时特定 B 细胞亚群的体内平衡中的作用。通过使用仅缺乏分泌型 IgM 的遗传缺陷小鼠（分泌型 μ 链缺陷型）、缺乏转换型 Ig 和高突变 IgM（激活诱导的胞嘧啶脱氨酶缺陷型）或完全无丙种球蛋白血症（AID(-/-)µS(-/-)），我们剖析了不同 Ig 类对与血清 Ig 丧失相关的 4 种表型的贡献：1）增加脾脏 B 细胞数量，主要是 B1 和边缘区 (MZ) B 细胞亚型；2）脾脏和肠系膜淋巴结中的生发中心 (GC) 增大；3）富含 IRF4(+)CD138(-)浆母细胞样细胞；以及 4）几种细胞亚群中 IgM 的过度表达。基于嵌合体的混合骨髓重建或 Ig 输注的补充实验，以及在无菌条件下饲养的小鼠的分析表明，存在一种负反馈机制，其中 MZ 和 B1 细胞数量受天然分泌型 Ig 的控制，这是免疫系统的内在特性的结果，而 GC 发育受分泌型 Ig 的间接控制，这些 Ig 限制触发 GC 反应的细菌种类。
