人生沒有用不到的經歷

今日讀到B細胞在淋巴結 T zone和B zone附近與Tfh cell 完成linked recognition，活化的B cell部分往medullary cord聚集為primary focus，部分回到primary lymphoid follicle增殖形成germinal center.....

下面接了一句我摸不著頭緒的
"Germinal center的plasma cell會進入medullary cord，或是離開淋巴結進入骨髓"

回到骨髓的用意是?
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這是Plasma cell homing。下圖顯示Naïve B cell被入侵的抗原活化後分化成Plasma cell的過程，Cell surface marker會變，參與分化的Transcription factor也會變，其中Blimp-1 drives antibody production。胞膜上的CXCR4在分化成熟的Plasma cell增加，其Ligand SDF-1 (Stromal cell derived factor-1 = CXCL12)由骨髓中的Stromal cell分泌，吸引Plasma cell至骨髓定居。骨髓是IgG-producing plasma cell最重要的藏身地，壽命數個月到數年，Plasma cell可在骨髓中製造抗體：

 
https://www.sciencedirect.com/science/article/pii/B978012397933900014X
Major plasma cell marker: CXCR4
Major plasma cell transcription factor: Blimp1, IRF4, XBP1

Plasma cell 主要Homing to骨髓，另一主要的Homing site是呼吸系統及消化系統黏膜下方的淋巴組織，骨髓與黏膜淋巴組織的Plasma cell會持續產生抗體直到該Plasma cell死亡。骨髓的Plasma cell主要產生IgG(也有IgM及少量IgA)，黏膜淋巴組織的Plasma cell產生IgA。

Plasma cell homing的細節請參閱下文：
https://www.ncbi.nlm.nih.gov/pubmed/14523388
Homing過程需要Plasma cell胞膜上的Integrin 與 Chemokine receptor，不同的Integrin與Chemokine receptor決定where a plasma cell is to be homing，即Homing site的細胞分泌Chemokines吸引Plasma cell前往定居。

 
Homing site的Epithelial cell或Stromal cell分泌Chemokines (如CXCL12, CCL25, CCL27, CCL28)吸引Antibody-secreting cell (ASC即發育成熟的Plasma cell)前往定居。
1. Homing to bone marrow需要Integrin a₄b₁(to its ligand VCAM1) + CXCR4 (to its ligand CXCL12)。 
1. Homing to mucosa lymphoid tissue需要Integrin a₄b₇(to its lignad MADCAM1) + CCR9 (to its ligand CCL25) and/or CCR10 (to its ligands CCL27 and CCL28)。
如下圖所示：
 
 

上圖Antigen challenge: Small intestine及Respiratory IgA-producing plasma cell是對抗共生菌。Systemic (non-mucosal) plasma cell可能發生在急性感染或慢性感染，臨床上急性感染如Mycoplasma pneumoniae(MP)感染，血中可測到Anti-MP IgM。Anti-MP IgM-producing plasma cells home to both the lung and bone marrow, but the antibody fails to combat the bacteria. 慢性感染如幽門桿菌(Helicobacter pylori, HP)感染，血中可測到Anti-HP IgG。Anti-HP IgG-producing plasma cells home to both the stomach and bone marrow, and likewise the antibody fails to eradicate the bacteria. 以抗生素殺菌(MP or HP)後，血中 anti-MP-IgM or anti-HP IgG 會逐漸消失。Anti-MP IgM can switch to IgG. Anti-MP IgG-producing plasma cells home to and stay in the bone marrow where the IgG is produced until the plasma cells die.