Department of Biomedical Science and Technology, University of Udine, Udine, Italy.
Blood. 2010 Apr 8;115(14):2810-7. doi: 10.1182/blood-2009-10-250126. Epub 2010 Jan 25.
The evidence of a tight spatial interaction between mast cells (MCs) and B lymphocytes in secondary lymphoid organs, along with the data regarding the abundance of MCs in several B-cell lymphoproliferative disorders prompted us to investigate whether MCs could affect the proliferation and differentiation of B cells. To this aim, we performed coculture assays using mouse splenic B cells and bone marrow-derived MCs. Both nonsensitized and activated MCs proved able to induce a significant inhibition of cell death and an increase in proliferation of naive B cells. Such proliferation was further enhanced in activated B cells. This effect relied on cell-cell contact and MC-derived interleukin-6 (IL-6). Activated MCs could regulate CD40 surface expression on unstimulated B cells and the interaction between CD40 with CD40 ligand (CD40L) on MCs, together with MC-derived cytokines, was involved in the differentiation of B cells into CD138(+) plasma cells and in selective immunoglobulin A (IgA) secretion. These data were corroborated by in vivo evidence of infiltrating MCs in close contact with IgA-expressing plasma cells within inflamed tissues. In conclusion, we reported here a novel role for MCs in sustaining B-cell expansion and driving the development of IgA-oriented humoral immune responses.
肥大细胞（MCs）与次级淋巴器官中的 B 淋巴细胞之间存在紧密的空间相互作用的证据，以及 MCs 在几种 B 细胞淋巴增生性疾病中丰富的数据，促使我们研究 MC 是否可以影响 B 细胞的增殖和分化。为此，我们使用鼠脾 B 细胞和骨髓来源的 MC 进行共培养实验。未致敏和激活的 MC 均被证明能够显著抑制细胞死亡并增加幼稚 B 细胞的增殖。这种增殖在激活的 B 细胞中进一步增强。这种效应依赖于细胞-细胞接触和 MC 衍生的白细胞介素 6（IL-6）。激活的 MC 可以调节未刺激 B 细胞表面的 CD40 表达，以及 MC 上的 CD40 与 CD40 配体（CD40L）之间的相互作用，同时 MC 衍生的细胞因子参与 B 细胞向 CD138（+）浆细胞分化和选择性免疫球蛋白 A（IgA）分泌。这些数据得到了体内证据的证实，即浸润的 MC 与炎症组织中表达 IgA 的浆细胞密切接触。总之，我们在这里报道了 MC 在维持 B 细胞扩增和驱动 IgA 定向体液免疫反应发展中的新作用。
