Unique ErkMAPkinase checkpoint signatures drive differential responses during the immature-mature B cell transition?

B淋巴细胞是一种能产生抗体的细胞，这种抗体在人体抵抗感染的过程中起着重要作用。为了对抗任何感染，大量随机不同的B细胞被制造出来。然而，这些B细胞中的许多细胞可以潜在地产生能够攻击体内分子（自身分子）的抗体，导致自身免疫性疾病，如风湿性关节炎。因此，免疫系统进化出了检查点，通过杀死在一个称为耐受的过程中附着在自身分子上的未成熟细胞来防止自身免疫B细胞的产生。相比之下，当成熟的耐受性B细胞遇到感染时，这些B细胞中的许多细胞发育成抗体分泌细胞来对抗疾病。此外，一些成为记忆B细胞，可以产生更快，更好的抗体反应，如果宿主再次感染这种疾病。?记忆？是开发破伤风和小儿麻痹症等疾病疫苗的基础。因此，本申请的目的是找出调节自身反应性B细胞的破坏和有用的B细胞特异性的保留的关键分子事件，因为这些的鉴定对于开发新的疫苗、癌症和自身免疫疗法具有明显的潜力。

B-lymphocytes are cells that produce proteins known as antibodies that play important roles in the body s fight against infection. In order to fight any infection, vast numbers of randomly different B cells are made. However, many of these B cells can potentially make antibodies capable of attacking molecules within the body (self molecules), resulting in autoimmune diseases like Rheumatoid Arthritis. The immune system has therefore evolved checkpoints to prevent production of autoimmune B cells by killing immature cells that attach themselves to self molecules in a process known as tolerance. By contrast, when mature tolerant B cells encounter infections, many of these B cells develop into antibody-secreting cells to fight the disease. In addition, some become memory B cells that can produce faster, better antibody responses if the host becomes re-infected with this same disease. ?Memory? is the basis underlying the development of vaccines against diseases such as tetanus and polio. The aim of this application, therefore, is to work out the key molecular events regulating destruction of autoreactive B cells and retention of useful B cell specificities as identification of these has obvious potential for the development of new vaccine, cancer and autoimmunity therapies.