Raman Vanitha S, Akondy Rama S, Rath Satyajit, Bal Vineeta, George Anna
National Institute of Immunology, New Delhi, India.
J Immunol. 2003 Dec 1;171(11):5876-81. doi: 10.4049/jimmunol.171.11.5876.
Ligation of CD27 on B cells has been shown to inhibit terminal differentiation of activated murine B cells into plasma cells. We show in this study that this inhibition is accompanied by an enhanced movement of activated B cells toward differentiation into memory cells. Treatment of mice with anti-CD27 during immunization leads to the generation of greater numbers of Ag-binding B cells in draining lymph nodes that persist for longer periods of time, and they contain a greater proportion of cells of a postgerminal center phenotype. Limiting dilution analyses reveal that they contain a higher frequency of cells that can be stimulated to secrete specific IgG, and adoptive transfer experiments confirm that they can generate higher secondary responses in carrier-primed recipients. Remarkably, significant secondary responses are also seen following primary immunization with a T-independent Ag in the presence of anti-CD27, confirming that ligation of CD27 on B cells during priming induces differentiation into the memory lineage. Treatment with anti-CD27 during priming also increases the average affinity of the secondary response, suggesting that high affinity clones generated early in a primary response may normally differentiate preferentially into plasma cells and are rescued from this fate by CD27 ligation. Anti-CD40 treatment shows similar effects in vivo. However, unlike CD27, CD40 coligation also enhances proliferation, survival, and isotype switching of LPS-stimulated B cells, suggesting that the two receptors may enhance commitment to B cell memory by different mechanisms, or that a common mechanism is used through both receptors that does not involve cell cycle control or survival.
已证明，B细胞上CD27的连接可抑制活化的小鼠B细胞向浆细胞的终末分化。我们在本研究中表明，这种抑制伴随着活化B细胞向记忆细胞分化的运动增强。在免疫期间用抗CD27治疗小鼠会导致引流淋巴结中产生更多数量的抗原结合B细胞，这些细胞持续时间更长，并且它们包含更大比例的生发中心后表型细胞。有限稀释分析表明，它们含有更高频率的可被刺激分泌特异性IgG的细胞，过继转移实验证实它们可以在载体致敏的受体中产生更高的二次反应。值得注意的是，在用非T细胞依赖性抗原进行初次免疫且存在抗CD27的情况下，也能观察到显著的二次反应，这证实了在启动过程中B细胞上CD27的连接可诱导向记忆谱系的分化。在启动过程中用抗CD27治疗还会增加二次反应的平均亲和力，这表明在初次反应早期产生的高亲和力克隆通常可能优先分化为浆细胞，并通过CD27连接从这种命运中被挽救。抗CD40治疗在体内显示出类似的效果。然而，与CD27不同，CD40共连接还增强了LPS刺激的B细胞的增殖、存活和同种型转换，这表明这两种受体可能通过不同机制增强对B细胞记忆的定向分化，或者通过不涉及细胞周期控制或存活的两种受体使用共同机制。
