Smith K G, Light A, Nossal G J, Tarlinton D M
The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria, Australia.
EMBO J. 1997 Jun 2;16(11):2996-3006. doi: 10.1093/emboj/16.11.2996.
Immunization with protein-containing antigens results in two types of antigen-specific B cell: antibody forming cells (AFCs) producing antibody of progressively higher affinity and memory lymphocytes capable of producing high affinity antibody upon re-exposure to antigen. The issue of the inter-relationship between affinity maturation of memory B cells and AFCs was addressed through analysis of single, antigen-specific B cells from the memory and AFC compartments during the primary response to a model antigen. Only 65% of splenic memory B cells were found capable of producing high affinity antibody, meaning that low affinity cells persist into this compartment. In contrast, by 28 days after immunization all AFCs produced high affinity antibody. We identified a unique, persistent sub-population of bone marrow AFCs containing few somatic mutations, suggesting they arose early in the response, yet highly enriched for an identical affinity-enhancing amino acid exchange, suggesting strong selection. Our results imply that affinity maturation of a primary immune response occurs by the early selective differentiation of high affinity variants into AFCs which subsequently persist in the bone marrow. In contrast, the memory B-cell population contains few, if any, cells from the early response and is less stringently selected.
用含蛋白质抗原进行免疫会产生两种抗原特异性B细胞：产生亲和力逐渐升高的抗体的抗体形成细胞（AFC），以及再次接触抗原时能够产生高亲和力抗体的记忆淋巴细胞。通过分析初次接触模型抗原时来自记忆和AFC区室的单个抗原特异性B细胞，研究了记忆B细胞和AFC亲和力成熟之间的相互关系。结果发现，只有65%的脾脏记忆B细胞能够产生高亲和力抗体，这意味着低亲和力细胞持续存在于该区室中。相比之下，免疫后28天时，所有AFC都产生了高亲和力抗体。我们鉴定出了骨髓AFC的一个独特的持续亚群，其体细胞突变很少，这表明它们在反应早期产生，但高度富集相同的亲和力增强氨基酸交换，这表明存在强烈的选择。我们的结果表明，初次免疫反应的亲和力成熟是通过高亲和力变体早期选择性分化为AFC来实现的，这些AFC随后在骨髓中持续存在。相比之下，记忆B细胞群体中几乎没有来自早期反应的细胞，并且选择也不那么严格。
