Blink Elizabeth J, Light Amanda, Kallies Axel, Nutt Stephen L, Hodgkin Philip D, Tarlinton David M
The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Australia.
J Exp Med. 2005 Feb 21;201(4):545-54. doi: 10.1084/jem.20042060. Epub 2005 Feb 14.
Immunization with a T cell-dependent antigen elicits production of specific memory B cells and antibody-secreting cells (ASCs). The kinetic and developmental relationships between these populations and the phenotypic forms they and their precursors may take remain unclear. Therefore, we examined the early stages of a primary immune response, focusing on the appearance of antigen-specific B cells in blood. Within 1 wk, antigen-specific B cells appear in the blood with either a memory phenotype or as immunoglobulin (Ig)G1 ASCs expressing blimp-1. The memory cells have mutated V(H) genes; respond to the chemokine CXCL13 but not CXCL12, suggesting recirculation to secondary lymphoid organs; uniformly express B220; show limited differentiation potential unless stimulated by antigen; and develop independently of blimp-1 expression. The antigen-specific IgG1 ASCs in blood show affinity maturation paralleling that of bone marrow ASCs, raising the possibility that this compartment is established directly by blood-borne ASCs. We find no evidence for a blimp-1-expressing preplasma memory compartment, suggesting germinal center output is restricted to ASCs and B220(+) memory B cells, and this is sufficient to account for the process of affinity maturation.
用依赖T细胞的抗原进行免疫会引发特异性记忆B细胞和抗体分泌细胞（ASC）的产生。这些细胞群体之间的动力学和发育关系，以及它们及其前体可能呈现的表型形式仍不清楚。因此，我们研究了初次免疫反应的早期阶段，重点关注血液中抗原特异性B细胞的出现。在1周内，抗原特异性B细胞出现在血液中，具有记忆表型或作为表达B淋巴细胞诱导成熟蛋白-1（Blimp-1）的免疫球蛋白（Ig）G1 ASC。记忆细胞具有突变的重链可变区（V(H)）基因；对趋化因子CXC趋化因子配体13（CXCL13）有反应，但对CXC趋化因子配体12（CXCL12）无反应，提示其再循环至二级淋巴器官；均一性表达B220；除非受到抗原刺激，分化潜能有限；且其发育独立于Blimp-1表达。血液中的抗原特异性IgG1 ASC显示出与骨髓ASC相似的亲和力成熟，这增加了该细胞区室直接由血源性ASC建立的可能性。我们没有发现存在表达Blimp-1的前浆细胞记忆细胞区室的证据，提示生发中心输出仅限于ASC和B220(+)记忆B细胞，而这足以解释亲和力成熟过程。
