Marks Ellen, Ortiz Carla, Pantazi Eirini, Bailey Charlotte S, Lord Graham M, Waldschmidt Thomas J, Noelle Randolph J, Elgueta Raul
Department of Mucosal Immunology, Division of Transplantation Immunology & Mucosal Biology, Guy's Hospital, King's College London , London , UK.
Department of Immune Regulation and Intervention, Division of Transplantation Immunology & Mucosal Biology, Guy's Hospital, King's College London , London , UK.
Front Immunol. 2016 Dec 23;7:643. doi: 10.3389/fimmu.2016.00643. eCollection 2016.
Retinoic acid (RA) plays an important role in the balance of inflammation and tolerance in T cells. Furthermore, it has been demonstrated that RA facilitates IgA isotype switching in B cells . However, it is unclear whether RA has a direct effect on T-independent B cell responses . To address this question, we generated a mouse model where RA signaling is specifically silenced in the B cell lineage. This was achieved through the overexpression of a dominant negative receptor α for RA (dnRARα) in the B cell lineage. In this model, we found a dramatic reduction in marginal zone (MZ) B cells and accumulation of transitional 2 B cells in the spleen. We also observed a reduction in B1 B cells in the peritoneum with a defect in the T-independent B cell response against 2,4,6-trinitrophenyl. This was not a result of inhibited development of B cells in the bone marrow, but likely the result of both defective expression of S1P in MZ B cells and a defect in the development of MZ and B1 B cells. This suggests that RARα expression in B cells is important for B cell frequency in the MZ and peritoneum, which is crucial for the generation of T-independent humoral responses.
视黄酸（RA）在T细胞炎症与耐受平衡中发挥重要作用。此外，已有研究表明RA促进B细胞中的IgA同种型转换。然而，RA是否对非T细胞依赖性B细胞反应有直接影响尚不清楚。为解决这个问题，我们构建了一个小鼠模型，其中RA信号在B细胞谱系中被特异性沉默。这是通过在B细胞谱系中过表达RA的显性负性受体α（dnRARα）来实现的。在这个模型中，我们发现脾脏边缘区（MZ）B细胞显著减少，过渡2型B细胞积累。我们还观察到腹膜中B1 B细胞减少，对2,4,6-三硝基苯的非T细胞依赖性B细胞反应存在缺陷。这不是骨髓中B细胞发育受抑制的结果，而可能是MZ B细胞中S1P表达缺陷以及MZ和B1 B细胞发育缺陷共同导致的。这表明B细胞中RARα的表达对于MZ和腹膜中的B细胞频率很重要，而这对于非T细胞依赖性体液反应的产生至关重要。
