Amitai Assaf, Mesin Luka, Victora Gabriel D, Kardar Mehran, Chakraborty Arup K
Chemical Engineering, Massachusetts Institute of TechnologyCambridge, MA, United States.
Institute for Medical Engineering and Science, Massachusetts Institute of TechnologyCambridge, MA, United States.
Front Microbiol. 2017 Sep 12;8:1693. doi: 10.3389/fmicb.2017.01693. eCollection 2017.
Germinal centers (GCs) are micro-domains where B cells mature to develop high affinity antibodies. Inside a GC, B cells compete for antigen and T cell help, and the successful ones continue to evolve. New experimental results suggest that, under identical conditions, a wide spectrum of clonal diversity is observed in different GCs, and high affinity B cells are not always the ones selected. We use a birth, death and mutation model to study clonal competition in a GC over time. We find that, like all evolutionary processes, diversity loss is inherently stochastic. We study two selection mechanisms, birth-limited and death limited selection. While death limited selection maintains diversity and allows for slow clonal homogenization as affinity increases, birth limited selection results in more rapid takeover of successful clones. Finally, we qualitatively compare our model to experimental observations of clonal selection in mice.
生发中心（GCs）是B细胞成熟以产生高亲和力抗体的微区域。在生发中心内，B细胞竞争抗原和T细胞辅助，成功的B细胞会继续进化。新的实验结果表明，在相同条件下，不同的生发中心会观察到广泛的克隆多样性，高亲和力B细胞并不总是被选中的细胞。我们使用一个出生、死亡和突变模型来研究生发中心随时间的克隆竞争。我们发现，与所有进化过程一样，多样性的丧失本质上是随机的。我们研究了两种选择机制，出生受限选择和死亡受限选择。虽然死亡受限选择维持了多样性，并随着亲和力的增加允许缓慢的克隆同质化，但出生受限选择会导致成功克隆更快地占据主导。最后，我们将我们的模型与小鼠克隆选择的实验观察进行了定性比较。
