Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
PLoS One. 2011;6(12):e27650. doi: 10.1371/journal.pone.0027650. Epub 2011 Dec 1.
Germinal centers (GCs) are complex dynamic structures that form within lymph nodes as an essential process in the humoral immune response. They represent a paradigm for studying the regulation of cell movement in the development of complex anatomical structures. We have developed a simulation of a modified cyclic re-entry model of GC dynamics which successfully employs chemotaxis to recapitulate the anatomy of the primary follicle and the development of a mature GC, including correctly structured mantle, dark and light zones. We then show that correct single cell movement dynamics (including persistent random walk and inter-zonal crossing) arise from this simulation as purely emergent properties. The major insight of our study is that chemotaxis can only achieve this when constrained by the known biological properties that cells are incompressible, exist in a densely packed environment, and must therefore compete for space. It is this interplay of chemotaxis and competition for limited space that generates all the complex and biologically accurate behaviors described here. Thus, from a single simple mechanism that is well documented in the biological literature, we can explain both higher level structure and single cell movement behaviors. To our knowledge this is the first GC model that is able to recapitulate both correctly detailed anatomy and single cell movement. This mechanism may have wide application for modeling other biological systems where cells undergo complex patterns of movement to produce defined anatomical structures with sharp tissue boundaries.
生发中心（GCs）是在淋巴结中形成的复杂动态结构，是体液免疫反应的重要过程。它们代表了研究细胞在复杂解剖结构发育过程中运动调节的范例。我们开发了一种改良的 GC 动力学循环再进入模型的模拟，该模型成功地利用趋化性来再现初级滤泡的解剖结构和成熟 GC 的发育，包括正确结构的套区、暗区和亮区。然后我们表明，正确的单细胞运动动力学（包括持续的随机游走和区带间穿越）作为纯粹的涌现特性源于该模拟。我们研究的主要观点是，只有当趋化性受到细胞不可压缩、存在于密集堆积的环境中以及必须因此竞争空间等已知生物学特性的限制时，趋化性才能实现这一点。正是趋化性和对有限空间的竞争的相互作用产生了这里描述的所有复杂和准确的生物学行为。因此，从一个在生物学文献中得到很好记录的单一简单机制，我们可以解释更高层次的结构和单细胞运动行为。据我们所知，这是第一个能够正确再现详细解剖结构和单细胞运动的 GC 模型。这种机制可能广泛应用于模拟其他生物学系统，在这些系统中，细胞经历复杂的运动模式，以产生具有锐利组织边界的定义解剖结构。
