Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Norway.
Autoimmunity. 2011 Aug;44(5):415-26. doi: 10.3109/08916934.2010.545847. Epub 2011 Feb 21.
Long-lived plasma cells (PCs) residing in the bone marrow (BM) are important producers of protective antibodies. However, when reacting against self-antigens, these PCs produce autoantibodies that contribute to progression of autoimmune diseases such as Sjögren's syndrome (SS). By using a murine model of primary SS, the NOD.B10.H2b mice, we characterized phenotype and generation of PCs at different stages of the pSS disease progression. In general, the PC population found in the NOD.B10.H2b mice expressed high amounts of MHCII, IgG, and BrdU. We further demonstrate the presence of both short- and long-lived PCs in autoimmune spleen and in autoimmune BM. A long-lived PC subset was also found in the spleen and BM of non-autoimmune BALB/c mice, which have not been treated with any immunological agent. Quantitative investigation of splenic and BM PCs revealed that in the NOD.B10.H2 mice, splenic PCs migrate not only to the BM but possibly also to the sites of inflammation. Finally, BM in the aged NOD.B10.H2b mice (40-week-old) presented significantly higher quantities of long-lived PCs than BM of BALB/c mice.
长寿命浆细胞(PCs)驻留在骨髓(BM)中,是产生保护性抗体的重要细胞。然而,当这些 PCs 针对自身抗原发生反应时,会产生自身抗体,从而导致自身免疫性疾病(如干燥综合征)的进展。通过使用原发性干燥综合征的小鼠模型,NOD.B10.H2b 小鼠,我们描述了 pSS 疾病进展的不同阶段中 PCs 的表型和生成。通常,在 NOD.B10.H2b 小鼠中发现的 PC 群体表达高水平的 MHCII、IgG 和 BrdU。我们进一步证明了在自身免疫性脾脏和自身免疫性 BM 中存在短寿命和长寿命 PCs。在未接受任何免疫试剂处理的非自身免疫性 BALB/c 小鼠的脾脏和 BM 中也发现了长寿命 PC 亚群。对脾脏和 BM PCs 的定量研究表明,在 NOD.B10.H2 小鼠中,脾脏 PCs 不仅迁移到 BM,而且可能迁移到炎症部位。最后,40 周龄的年老 NOD.B10.H2b 小鼠的 BM 中长寿命 PCs 的数量明显高于 BALB/c 小鼠的 BM。