Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu, Shizuoka, Japan.
Am J Respir Cell Mol Biol. 2012 Jun;46(6):773-80. doi: 10.1165/rcmb.2011-0329OC. Epub 2012 Jan 20.
Lung dendritic cells (LDCs) are primary antigen-presenting cells that develop IgA-producing plasma cells in the lung through class switch recombination (CSR) in naive B cells. Recently, the major LDC subsets were found to comprise CD103(-)CD11b(high) LDCs (CD11b(high) LDCs) and CD103(+)CD11b(low or negative) LDCs (CD103(+) LDCs), but their abilities to induce IgA production have not been defined. Under T cell-dependent (T-D) and T cell-independent (T-ID) conditions, we compared the abilities of these two LDC populations to induce IgA. CD11b(high) or CD103(+) LDCs obtained from BALB/c mice were cocultured with naive IgD(+) B cells in the presence of LPS, with or without anti-CD40 monoclonal antibody (mAb) (i.e., T-D and T-ID coculture conditions, respectively). Under both T-D and T-ID conditions, CD11b(high) LDCs induced significantly greater amounts of IgA production, together with a significantly higher mRNA expression of activation-induced cytidine deaminase, than did CD103(+) LDCs. However, the protein expression of a proliferation-inducing ligand, B cell-activating factor of the tumor necrosis family, or retinaldehyde dehydrogenase-1 did not differ between the two LDC subsets. CD11b(high) LDCs displayed a significantly greater capacity to secrete IL-6 and IL-10 in response to LPS, with or without anti-CD40 mAb. Moreover, the IgA production induced by CD11b(high) LDCs in T-D coculture was attenuated by neutralizing both IL-6 and IL-10. These findings suggest that, of the two major LDCs, CD11b(high) LDCs more efficiently induce IgA than do CD103(+) LDCs, possibly through their potent capacity to produce IgA-inducing cytokines.
肺树突状细胞 (LDC) 是主要的抗原呈递细胞,可通过幼稚 B 细胞的类别转换重组 (CSR) 在肺部产生 IgA 产生的浆细胞。最近,主要的 LDC 亚群被发现包括 CD103(-)CD11b(high) LDCs (CD11b(high) LDCs) 和 CD103(+)CD11b(low 或阴性) LDCs (CD103(+) LDCs),但其诱导 IgA 产生的能力尚未确定。在 T 细胞依赖性 (T-D) 和 T 细胞非依赖性 (T-ID) 条件下,我们比较了这两种 LDC 群体诱导 IgA 的能力。从 BALB/c 小鼠中获得的 CD11b(high) 或 CD103(+) LDC 与幼稚 IgD(+) B 细胞在 LPS 存在下共培养,有或没有抗 CD40 单克隆抗体 (mAb)(即 T-D 和 T-ID 共培养条件)。在 T-D 和 T-ID 条件下,CD11b(high) LDC 诱导产生的 IgA 量显著高于 CD103(+) LDC,同时活化诱导胞嘧啶脱氨酶的 mRNA 表达也显著升高。然而,两种 LDC 亚群的增殖诱导配体、肿瘤坏死因子家族的 B 细胞激活因子或视黄醛脱氢酶-1 的蛋白表达没有差异。CD11b(high) LDC 对 LPS 的反应显示出更强的分泌 IL-6 和 IL-10 的能力,有或没有抗 CD40 mAb。此外,在 T-D 共培养中,CD11b(high) LDC 诱导的 IgA 产生可通过中和 IL-6 和 IL-10 而减弱。这些发现表明,在两种主要的 LDC 中,CD11b(high) LDC 比 CD103(+) LDC 更有效地诱导 IgA,可能是通过其产生 IgA 诱导细胞因子的强大能力。