It is now appreciated that in addition to their role in humoral immunity B cells also exert regulatory mechanisms that lead to attenuation of inflammatory responses. The concept of B cell regulation became well-recognized when mice deficient in B cells due to genetic disruption were shown to be refractory to recovery from the signs of experimental autoimmune encephalomyelitis (EAE), the mouse model of multiple sclerosis. This seminal study spurred the search for B cell regulatory phenotypes and mechanisms of action. Our approach was to utilize differential B cell depletion with anti-CD20 to retain B cells whose presence were required to achieve EAE recovery. Utilizing flow cytometry, adoptive cell therapy and genetic approaches, we discovered a new B cell subset that upon adoptive transfer into B cell-deficient mice, was sufficient to promote EAE recovery. This B cell subset is IgM⁺, but due to low/negative IgD cell surface expression it was named B cell IgD low (BD_L). Mechanistically, we found that in the absence of BD_L, the absolute cell number of CD4⁺ Foxp3⁺ T regulatory cells (Treg), essential for immune tolerance, were significantly reduced. Furthermore, we found that BD_L expression of glucocorticoid-induced tumor necrosis factor ligand (GITRL) was essential for induction of Treg proliferation and maintenance of their homeostasis. Thus, we have identified a new B cell subset that is critical for immunological tolerance through interactions with Treg.

现在认识到除了它们在体液免疫中的作用之外，B细胞还发挥导致炎症反应减弱的调节机制。当由于遗传破坏而缺乏 B 细胞的小鼠被证明难以从多发性硬化症小鼠模型实验性自身免疫性脑脊髓炎 (EAE) 的迹象中恢复时，B 细胞调节的概念得到了广泛认可。这项开创性研究激发了对 B 细胞调节表型和作用机制的探索。我们的方法是利用抗 CD20 的差异 B 细胞消耗来保留 B 细胞，这些 B 细胞的存在是实现 EAE 恢复所必需的。利用流式细胞术、过继细胞疗法和遗传方法，我们发现了一个新的 B 细胞亚群，它在过继转移到 B 细胞缺陷小鼠中后，足以促进 EAE 恢复。这个 B 细胞亚群是 IgM⁺，但由于低/阴性 IgD 细胞表面表达，它被命名为 B 细胞 IgD 低 (BD _L )。从机制上讲，我们发现在没有 BD _L的情况下，免疫耐受所必需的 CD4 ⁺  Foxp3 ⁺ T 调节细胞 (Treg)的绝对细胞数显着减少。此外，我们发现糖皮质激素诱导的肿瘤坏死因子配体 (GITRL) 的BD _L表达对于诱导 Treg 增殖和维持其稳态至关重要。因此，我们已经确定了一个新的 B 细胞亚群，它通过与 Treg 的相互作用对免疫耐受至关重要。