Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102, China.
Proc Natl Acad Sci U S A. 2021 Jul 6;118(27). doi: 10.1073/pnas.2106754118.
Immunoglobulin A (IgA)-producing plasma cells derived from conventional B cells in the gut play an important role in maintaining the homeostasis of gut flora. Both T cell-dependent and T cell-independent IgA class switching occurs in the lymphoid structures in the gut, whose formation depends on lymphoid tissue inducers (LTis), a subset of innate lymphoid cells (ILCs). However, our knowledge on the functions of non-LTi helper-like ILCs, the innate counter parts of CD4 T helper cells, in promoting IgA production is still limited. By cell adoptive transfer and utilizing a unique mouse strain, we demonstrated that the generation of IgA-producing plasma cells from B cells in the gut occurred efficiently in the absence of both T cells and helper-like ILCs and without engaging TGF-β signaling. Nevertheless, B cell recruitment and/or retention in the gut required functional NKp46CCR6 LTis. Therefore, while CCR6 LTis contribute to the accumulation of B cells in the gut through inducing lymphoid structure formation, helper-like ILCs are not essential for the T cell-independent generation of IgA-producing plasma cells.
肠道中源自常规 B 细胞的分泌型免疫球蛋白 A(IgA)浆细胞在维持肠道菌群稳态方面发挥着重要作用。T 细胞依赖性和非依赖性 IgA 类别转换均发生在肠道的淋巴组织中,其形成依赖于淋巴组织诱导物(LTis),即先天淋巴样细胞(ILCs)的一个子集。然而,我们对于非 LTIs 辅助样 ILCs(CD4 T 辅助细胞的先天对应物)在促进 IgA 产生中的功能的了解仍然有限。通过细胞过继转移和利用一种独特的小鼠品系,我们证明在没有 T 细胞和辅助样 ILCs且不涉及 TGF-β信号的情况下,肠道中 B 细胞能够有效地从 IgA 产生浆细胞。然而,B 细胞在肠道中的募集和/或保留需要功能性 NKp46CCR6 LTis。因此,虽然 CCR6 LTis 通过诱导淋巴组织形成有助于 B 细胞在肠道中的积累,但辅助样 ILCs对于 T 细胞非依赖性 IgA 产生浆细胞的生成并非必需。