Gamma delta T cells act as rheostats to modulate early B cell response

描述(申请人提供)：建立抗体反应是所有脊椎动物使用的主要免疫防御机制。同样，几乎所有的疫苗接种都是通过诱导抗体反应来起作用的。然而，并不是所有的抗体反应都具有保护性。有时，产生的抗体要么数量太少，要么亲和力太低--这些类型的 回应是无效的。矛盾的是，强烈的抗体反应可能也不能保护宿主。通常，早期旺盛的抗体反应与未能产生在以后清除感染和建立持续感染方面更有效的抗体有关。在细菌(例如莱姆病)、病毒(例如疱疹)和寄生虫(例如弓形虫)感染中观察到了这种现象。因此，抗体反应要么太弱，要么太强，就不能起到保护作用，甚至可能弊大于利；只有恰到好处的反应才能起到整体保护作用(金发女郎效应)。诱导抗体反应的方法已经被很好地记录下来了。然而，目前还完全不清楚如何调节抗体反应的强度，以最大限度地发挥保护作用。由于缺乏对增强抗体应答规律的了解，有效疫苗的合理设计仍然无法实现，慢性感染的预防和治疗仍然无效。这一应用是基于我们最近的发现，即γδT细胞可能是唯一适合于调节早期B细胞反应强度的细胞，试图建立检验这一假说的基础。我们的最终目标是确定调节抗体反应大小的原则，希望发现可用于疫苗开发和治疗慢性感染的新的干预点。

DESCRIPTION (provided by applicant): Mounting an antibody response is a major immune defense mechanism used by all vertebrates. Similarly, nearly all vaccinations work by inducing an antibody response. However, not all antibody responses are protective. Sometimes, the antibodies that are generated are either too few in number, or too low in affinity - these kinds of responses are ineffective. Paradoxically, a strong antibody response may not protect the host either. Often, an exuberant early antibody response is associated with a failure to produce antibodies that are more effective in clearing the infection later on and the establishment of persistent infections. This phenomenon has been observed in bacterial (e.g. Lyme disease), viral (e.g. Herpes) and parasitic (e.g. Toxoplasma gondii) infections. Thus, an antibody response that is either too weak or too strong is not protective and may even do more harm than good; only the response, which is "just right", has the overall protective effect (the Goldilocks effect). The way to induce an antibody response has been well documented. However it is not at all clear how to regulate the strength of an antibody response in order to maximize protection. Because the lack understanding of the rules of augmenting antibody response, the rational design of effective vaccines remains unachievable and the prevention and treatment of chronic infections remain ineffective. This application, which is based on our recent findings suggesting γδ T cells may be uniquely suited to modulate the strength of early B cell response, seeks to establish the basis to test this hypothesis. Our ultimate goal is to identiy the principles that regulate the magnitude of antibody response in hopes of uncovering new points of intervention that can be used in vaccine development as well as to treat chronic infections.