Department of Immunology, Eötvös Loránd University, Budapest, Hungary.
MTA-SE Momentum Molecular Oncohematology Research Group, First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Front Immunol. 2020 Sep 29;11:565458. doi: 10.3389/fimmu.2020.565458. eCollection 2020.
Complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) of myeloid cells are known for long to participate in actin linked functions like phagocytosis, adhesion, and migration. The expression and role of these two β-integrins however, in human B lymphocytes have only scarcely been studied so far, although it has been shown recently that CD11c B cells are mainly memory cells. In our systematic study we investigated B cells isolated from tonsils and peripheral blood of healthy donors. We found, that while only 5% of resting tonsillar B cells expressed CD11c, their number increased up to 26% after 3 days of BCR stimulation. Lower, but still remarkable percentage of B lymphocytes were positive for CD11c after stimulation via TLR9 alone or via TLR9 and BCR simultaneously. At the same time, we detected no significant expression of CD11b on resting or activated tonsillar B cells. Blood B lymphocytes showed a similar expression pattern of both β-integrins. We demonstrated that CD11c molecules appearing on the surface of B cells are newly synthesized, reaching the number of 9,500 per activated B cell. We found that CR4 expressing B cells belong to the memory pool and the increase of CD11c expression on tonsillar B cells upon BCR mediated activation occurs parallel with class switching. Analysis of the function of CD11c revealed, that this β-integrin contributes to the adhesion and migration of activated B lymphocytes. We also demonstrated that the CR4 mediated adhesion promotes the proliferation of the BCR activated cells. Our studies are the first to demonstrate that CD11c expressed on BCR-activated human B cells are not only passive markers but functional drivers of memory B cell responses.
髓样细胞的补体受体 CR3（CD11b/CD18）和 CR4（CD11c/CD18）长期以来一直被认为参与肌动蛋白连接的功能，如吞噬作用、黏附和迁移。然而，这两种 β 整合素在人类 B 淋巴细胞中的表达和作用迄今为止研究甚少，尽管最近已经表明 CD11c B 细胞主要是记忆细胞。在我们的系统研究中，我们研究了从健康供体的扁桃体和外周血中分离的 B 细胞。我们发现，静止的扁桃体 B 细胞中只有 5%表达 CD11c，但其数量在 BCR 刺激 3 天后增加到 26%。刺激 TLR9 单独或同时刺激 TLR9 和 BCR 后，B 淋巴细胞中 CD11c 阳性的比例较低，但仍相当可观。与此同时，我们在静止或激活的扁桃体 B 细胞上未检测到 CD11b 的显著表达。血液 B 淋巴细胞表现出两种β整合素相似的表达模式。我们证明，出现在 B 细胞表面的 CD11c 分子是新合成的，每个激活的 B 细胞达到 9500 个。我们发现，表达 CR4 的 B 细胞属于记忆池，BCR 介导的激活后扁桃体 B 细胞中 CD11c 表达的增加与类别转换平行发生。对 CD11c 功能的分析表明，这种β整合素有助于激活 B 淋巴细胞的黏附和迁移。我们还证明，CR4 介导的黏附促进了 BCR 激活细胞的增殖。我们的研究首次表明，在 BCR 激活的人类 B 细胞上表达的 CD11c 不仅是被动标志物，而且是记忆 B 细胞反应的功能驱动因素。
