Pascual D W, Riccardi C, Csencsits-Smith K
Department of Veterinary Molecular Biology, Montana State University, Bozeman, Montana, USA.
Mucosal Immunol. 2008 Jan;1(1):68-77. doi: 10.1038/mi.2007.2.
Understanding the role of homing receptors could aid vaccine strategies for developing distal mucosal immunity. Infection studies have revealed that immune intestinal B cells use alpha(4)beta(7) homing receptors, but their role in subsequent oral immunization with soluble antigens is unknown. To assess the influence of L-selectin and alpha(4)beta(7) on distal B cells following oral cholera toxin (CT) immunization, L-selectin-deficient (L-Sel(-/-)) IgA anti-CT-B-specific B cells were enhanced 30-, 9.2-, and 3.5-fold in head and neck lymph nodes (HNLNs), nasal-associated lymphoid tissue, and nasal passages (NPs), respectively, vs. L-Sel(+/+) mice. Cell-sorted intestinal and NP IgA antibody-forming cells (AFCs) were mostly alpha(4)beta(7)(+), unlike HNLN L-Sel(-/-) IgA and IgG anti-CT-B AFCs that were alpha(E)beta(7)(+), contrasting with L-Sel(+/+) HNLN IgA AFCs that were mostly alpha(4)beta(7)(+). In vitro studies revealed that L-Sel(-/-) HNLN B cells preferentially expressed alpha(E) following polyclonal stimulation. These studies show that HNLN B cells express alpha(E)beta(7) in the absence of L-selectin to sustain distal IgA responses.
了解归巢受体的作用有助于制定增强远端黏膜免疫的疫苗策略。感染研究表明,免疫肠道B细胞利用α(4)β(7)归巢受体,但它们在随后用可溶性抗原进行口服免疫中的作用尚不清楚。为了评估口服霍乱毒素(CT)免疫后L-选择素和α(4)β(7)对远端B细胞的影响,与L-Sel(+/+)小鼠相比,L-选择素缺陷(L-Sel(-/-))的IgA抗CT-B特异性B细胞在头颈部淋巴结(HNLN)、鼻相关淋巴组织和鼻道(NP)中分别增强了30倍、9.2倍和3.5倍。细胞分选的肠道和NP IgA抗体形成细胞(AFC)大多为α(4)β(7)(+),这与HNLN L-Sel(-/-) IgA和IgG抗CT-B AFC不同,后者为α(E)β(7)(+),与大多为α(4)β(7)(+)的L-Sel(+/+) HNLN IgA AFC形成对比。体外研究表明,L-Sel(-/-) HNLN B细胞在多克隆刺激后优先表达α(E)。这些研究表明,在缺乏L-选择素的情况下,HNLN B细胞表达α(E)β(7)以维持远端IgA反应。