Germinal Center and Extrafollicular B Cell Responses in Vaccination, Immunity, and Autoimmunity.
Germinal Center and Extrafollicular B Cell Responses in Vaccination, Immunity, and Autoimmunity.
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疫苗接种，免疫和自身免疫性中的生发中心和流体外B细胞反应。
DOI：
10.1016/j.immuni.2020.11.006
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发表时间：
2020-12-15
期刊：
影响因子：
32.4
通讯作者：
Shlomchik MJ
中科院分区：
文献类型：
--
作者：
Elsner RA;Shlomchik MJ
激活的B细胞参与滤泡外（EF）或生发中心（GC）反应。典型反应包括由EF位点产生的未突变浆细胞的短波，随后是产生GC的体细胞突变记忆B细胞（MBC）和长寿命浆细胞。然而，体细胞超突变和亲和力成熟可以在两个位点发生，并且在GC形成之前产生相当大部分的MBC。感染反应的范围从持续数月的GC反应到具有GC显性抑制的持续EF反应。在这里，我们回顾了目前的理解EF和GC响应的功能输出和促进它们的分子开关。我们讨论了调节这些反应的幅度和持续时间的信号，并概述了知识和调查的重要领域的差距。了解这些分子开关对于疫苗开发、疫苗效力的解释和自身免疫性疾病的治疗至关重要。B细胞反应跟踪向生发中心或滤泡外反应。毛囊外反应越来越被认为是某些感染和自身免疫的主导模式。Elsner和Shlomchik回顾了这两种反应类型，并讨论了对免疫、疫苗设计和疾病分层及治疗的影响。
Activated B cells participate in either extrafollicular (EF) or germinal center (GC) responses. Canonical responses are composed of a short wave of unmutated plasma cells arising from EF sites, followed by GC producing somatically mutated memory B cells (MBC) and long-lived plasma cells. However, somatic hypermutation and affinity maturation can take place at both sites, and a substantial fraction of MBC are produced prior to GC formation. Infection responses range from GC responses that persist for months, to persistent EF responses with dominant suppression of GCs. Here we review the current understanding of the functional output of EF and GC responses and the molecular switches promoting them. We discuss the signals that regulate the magnitude and duration of these responses, and outline gaps in knowledge and important areas of inquiry. Understanding such molecular switches will be critical for vaccine development, interpretation of vaccine efficacy and the treatment for autoimmune diseases. B cell responses track towards either germinal center or extrafollicular responses. The extrafollicular response is increasingly being appreciated as a dominant mode in certain infections and in autoimmunity. Elsner and Shlomchik review these two response types and discuss the implications for immunity, vaccine design and disease stratification and therapy.
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