Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
J Leukoc Biol. 2019 Mar;105(3):507-518. doi: 10.1002/JLB.1A0517-172RR. Epub 2018 Dec 21.
B cell development is regulated by stromal cells (SCs) that form a supportive microenvironment. These SCs along with other cell types produce cytokines, chemokines, and adhesion molecules that guide B cell commitment and differentiation. BM, spleen (Sp), and the gut lamina propria (LP) constitute distinctive anatomical compartments that support B cell differentiation. In order to characterize and compare the signals necessary to generate IgA B cells, we developed an in vitro system to co-culture gut LP, BM, or Sp-derived SCs with B lineage cells. Using this co-culture system, we found that gut LP SCs promote IgA B cell accumulation through the production of soluble stimulatory factors. In contrast to gut LP SCs, BM and splenic SCs were found to impair IgA B cell accumulation in vitro. Taken together, these observations provide new insights into how SCs derived from different anatomical locations shape IgA B cell responses.
B 细胞的发育受基质细胞（SCs）的调节，这些细胞形成支持性的微环境。这些 SC 与其他细胞类型一起产生细胞因子、趋化因子和黏附分子，指导 B 细胞的定型和分化。骨髓（BM）、脾脏（Sp）和肠道固有层（LP）构成了支持 B 细胞分化的独特解剖隔室。为了描述和比较产生 IgA B 细胞所需的信号，我们开发了一种体外共培养肠道 LP、BM 或 Sp 来源的 SC 与 B 细胞系的系统。使用这种共培养系统，我们发现肠道 LP SC 通过产生可溶性刺激因子促进 IgA B 细胞的积累。与肠道 LP SC 不同，BM 和脾 SC 被发现体外会损害 IgA B 细胞的积累。总之，这些观察结果为不同解剖部位来源的 SC 如何塑造 IgA B 细胞反应提供了新的见解。
