Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
Front Immunol. 2020 Apr 17;11:637. doi: 10.3389/fimmu.2020.00637. eCollection 2020.
The production of antibody-secreting plasma cells and memory B cells requires the interaction of T follicular helper (Tfh) cells with B cells in the follicle and is modulated by T follicular regulatory (Tfr) cells. We compare the effects of Tfr cells in an model of bystander Tfh function in the absence of BCR engagement and in a model in which mimics cognate T-B interactions in which the BCR is engaged. In the absence of Tfr cells, Tfh cells from primed mice induce naive B cell differentiation into GC B cells and class switch recombination (CSR) in the presence of anti-CD3 alone or anti-CD3/IgM in a contact-dependent manner. Addition of primed Tfr cells efficiently suppressed GC B cell proliferation, differentiation and CSR in the anti-CD3 alone cultures, but only moderately suppressed BCR-stimulated B cells. When stimulated with anti-CD3 alone, IL-4 is critical for the induction of GC B cells and CSR. IL-21 plays a minimal role in GC B cell differentiation, but a greater role in switching. When the BCR is engaged, IL-4 is primarily required for switching and IL-21 only modestly affects switching. CD40L expression was critical for Tfh-mediated B cell proliferation/differentiation in the absence of B cell engagement. When the BCR was engaged, proliferation of CD40 deficient B cells was partially restored, but was susceptible to suppression by Tfr. These studies suggest that Tfr suppressor function is complex and is modulated by BCR signaling and CD40-CD40L interactions.
产生分泌抗体的浆细胞和记忆 B 细胞需要滤泡辅助性 T（Tfh）细胞与滤泡中的 B 细胞相互作用，并受滤泡调节性 T（Tfr）细胞的调节。我们比较了 Tfr 细胞在两种模型中的作用，一种是在没有 B 细胞受体（BCR）结合的情况下旁观者 Tfh 功能的模型，另一种是模拟 BCR 结合的同源 T-B 相互作用的模型。在没有 Tfr 细胞的情况下，来自已激活小鼠的 Tfh 细胞在单独使用抗 CD3 或抗 CD3/IgM 的情况下，以接触依赖的方式诱导幼稚 B 细胞分化为 GC B 细胞和类别转换重组（CSR）。添加已激活的 Tfr 细胞可有效地抑制单独使用抗 CD3 培养物中的 GC B 细胞增殖、分化和 CSR，但对 BCR 刺激的 B 细胞的抑制作用仅适度。当单独用抗 CD3 刺激时，IL-4 对于诱导 GC B 细胞和 CSR 至关重要。IL-21 在 GC B 细胞分化中作用不大，但在转换中作用更大。当 BCR 被激活时，IL-4 主要用于转换，而 IL-21 仅适度影响转换。CD40L 表达对于在没有 B 细胞结合的情况下 Tfh 介导的 B 细胞增殖/分化至关重要。当 BCR 被激活时，CD40 缺陷 B 细胞的增殖部分得到恢复，但易受 Tfr 的抑制。这些研究表明，Tfr 抑制功能复杂，并受 BCR 信号和 CD40-CD40L 相互作用的调节。
