Department of Mathematics, Bar Ilan University, Ramat Gan, Israel.
Front Immunol. 2023 Sep 18;14:1166116. doi: 10.3389/fimmu.2023.1166116. eCollection 2023.
H chain rearrangement in B cells is a two-step process where first binds , and only then is joined to the complex. As such, there is no direct rearrangement between and .
Nevertheless, we here show that the JH combinations frequency in humans deviates from the one expected based on each gene usage frequency. This bias is observed mainly in functional rearrangements, and much less in out-of-frame rearrangements. The bias cannot be explained by preferred binding for genes or a preferred reading frame. Preferred combinations are shared between donors.
These results suggest a common structural mechanism for these biases. Through development, thepreferred combinations evolve during peripheral selection to become stronger, but less shared. We propose that peripheral Heavy chain usage is initially shaped by a structural selection before the naive B cellstate, followed by pathogen-induced selection for host specific - pairs.
B 细胞中的重链重排在第一阶段 与 结合，然后 才与复合物结合，是一个两步过程。因此， 和 之间没有直接的重排。
然而，我们在这里表明，人类的 JH 组合频率偏离了基于每个基因使用频率的预期值。这种偏差主要发生在功能重排中，而在框架外重排中则较少。这种偏差不能用 基因的优先结合或首选阅读框来解释。首选的 组合在供体之间共享。
这些结果表明这些偏差存在共同的结构机制。在发育过程中，在外周选择过程中，首选的 组合会变得更强，但共享性降低。我们提出，在幼稚 B 细胞状态之前，通过结构选择来初始塑造外周 Heavy 链使用，然后是针对宿主特异性 - 对的病原体诱导选择。
