Chen Qiuyan, Mosovsky Kara L, Ross A Catharine
Department of Nutritional Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Clin Vaccine Immunol. 2011 Jun;18(6):1015-20. doi: 10.1128/CVI.00004-11. Epub 2011 Apr 6.
All-trans-retinoic acid (RA) promotes the maturation and differentiation of B cells, which are known as a type of professional antigen-presenting cells. We show here that CD1d, a major histocompatibility complex class I-like molecule that presents lipid antigens, is expressed in the mouse spleen B cells and is increased by RA. Thus, we hypothesized that RA and the CD1d ligand, α-galactosylceramide (αGalCer), could interact to promote the differentiation, maturation, and antibody response of antigen-activated B cells. In isolated B cells, αGalCer alone markedly stimulated, and RA further increased B cell proliferation, synergizing with the B cell antigen receptor ligation via anti-μ antibody (P < 0.05). The significantly increased cell proliferation stimulated by αGalCer was abrogated in the B cells of CD1d-null mice. RA alone and combined with αGalCer also promoted B cell differentiation by the enrichment of sIgG1-, CD138-, and PNA/Fas-positive B cells (P < 0.05), suggesting a plasmacytic cell differentiation. In vivo, wild-type mice treated with RA and/or αGalCer during primary immunization with tetanus toxoid produced a higher serum anti-tetanus IgG response and had more bone marrow anti-tetanus antibody-secreting cells as determined by enzyme-linked immunospot assay (P < 0.05) in the secondary response, a finding indicative of heightened long-term memory; however, the increased antibody secretion after αGalCer treatment was abolished in CD1d-null mice. We provide evidence here that RA, together with αGalCer, can effectively regulate B cell proliferation and differentiation, ultimately promoting a more efficient antibody response to protein antigen. The results suggest that the combination of RA and αGalCer could be a useful adjuvant combination in vaccine strategies.
全反式维甲酸（RA）可促进B细胞的成熟和分化，B细胞是一种已知的专职抗原呈递细胞。我们在此表明，CD1d是一种呈递脂质抗原的主要组织相容性复合体I类样分子，在小鼠脾脏B细胞中表达，并可被RA上调。因此，我们推测RA与CD1d配体α-半乳糖神经酰胺（αGalCer）可能相互作用，以促进抗原激活的B细胞的分化、成熟和抗体反应。在分离的B细胞中，单独的αGalCer可显著刺激细胞，而RA通过抗μ抗体与B细胞抗原受体连接协同作用，进一步增加B细胞增殖（P < 0.05）。在CD1d基因敲除小鼠的B细胞中，αGalCer刺激引起的显著细胞增殖被消除。单独的RA以及与αGalCer联合使用还可通过富集sIgG1、CD138和PNA/Fas阳性B细胞促进B细胞分化（P < 0.05），提示浆细胞样细胞分化。在体内，用破伤风类毒素进行初次免疫期间接受RA和/或αGalCer治疗的野生型小鼠，在二次反应中产生了更高的血清抗破伤风IgG反应，并且通过酶联免疫斑点测定法测定，骨髓中抗破伤风抗体分泌细胞更多（P < 0.05），这一发现表明长期记忆增强；然而，αGalCer治疗后抗体分泌的增加在CD1d基因敲除小鼠中被消除。我们在此提供证据表明，RA与αGalCer一起可有效调节B细胞增殖和分化，最终促进对蛋白质抗原更有效的抗体反应。结果表明，RA和αGalCer的组合可能是疫苗策略中一种有用的佐剂组合。
