B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo
B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo
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DOI：
10.1073/pnas.0802968105
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发表时间：
2008-06-17
影响因子：
11.1
通讯作者：
Batista, Facundo D.
中科院分区：
文献类型：
--
作者：
Barral, Patricia;Eckl-Dorna, Julia;Batista, Facundo D.
高度调节的B细胞活化是产生保护免受病原体感染所必需的特异性抗体所必需的。这一过程是由抗原通过B细胞受体（BCR）的特异性识别启动的，导致早期细胞内信号传导，随后是T细胞辅助的晚期募集。在这项研究中，我们证明，特异性BCR摄取的CD 1d限制性抗原是一种有效的手段，增强不变的自然杀伤T（iNKT）依赖性B细胞在体内的反应。该机制在广泛的抗原亲和力范围内有效，但依赖于超过BCR介导的内化和颗粒抗原脂质的CD 1d依赖性呈递所需的严格调节的亲合力阈值。随后，iNKT细胞提供刺激B细胞增殖和分化所需的帮助。iNKT刺激的B细胞在滤泡外病灶内发育，并介导高滴度特异性IgM和早期类别转换抗体的产生。因此，我们已经证明，响应于颗粒抗原脂质，iNKT细胞被募集用于辅助B细胞活化，导致特异性抗体应答的增强。我们提出，这种机制可能会加强适应性免疫反应，对病原体在体内。
Highly regulated activation of B cells is required for the production of specific antibodies necessary to provide protection from pathogen infection. This process is initiated by specific recognition of antigen through the B cell receptor (BCR), leading to early intracellular signaling followed by the late recruitment of T cell help. In this study we demonstrate that specific BCR uptake of CD1d-restricted antigens represents an effective means of enhancing invariant natural killer T (iNKT)-dependent B cell responses in vivo. This mechanism is effective over a wide range of antigen affinities but depends on exceeding a tightly regulated avidity threshold necessary for BCR-mediated internalization and CD1d-dependent presentation of particulate antigenic lipid-Subsequently, iNKT cells provide the help required for stimulating B cell proliferation and differentiation. iNKT-stimulated B cells develop within extrafollicular foci and mediate the production of high titers of specific IgM and early class-switched antibodies. Thus, we have demonstrated that in response to particulate antigenic lipids iNKT cells are recruited for the assistance of B cell activation, resulting in the enhancement of specific antibody responses. We propose that such a mechanism may operate to potentiate adaptive immune responses against pathogens in vivo.